Coupled hydraulics and carbon economy underlie age-related growth decline and revitalisation of sand-fixing shrubs after crown removal.

Crown removal revitalises sand-fixing shrubs that show declining vigour with age in drought-prone environments; however, the underlying mechanisms are poorly understood. Here, we addressed this knowledge gap by comparing the growth performance, xylem hydraulics and plant carbon economy across different plant ages (10, 21 and 33 years) and treatments (control and crown removal) using a representative sand-fixing shrub (Caragana microphylla Lam.) in northern China. We found that growth decline with plant age was accompanied by simultaneous decreases in soil moisture, plant hydraulic efficiency and photosynthetic capacity, suggesting that these interconnected changes in plant water relations and carbon economy were responsible for this decline. Following crown removal, quick resprouting, involving remobilisation of root nonstructural carbohydrate reserves, contributed to the reconstruction of an efficient hydraulic system and improved plant carbon status, but this became less effective in older shrubs. These age-dependent effects of carbon economy and hydraulics on plant growth vigour provide a mechanistic explanation for the age-related decline and revitalisation of sand-fixing shrubs. This understanding is crucial for the development of suitable management strategies for shrub plantations constructed with species having the resprouting ability and contributes to the sustainability of ecological restoration projects in water-limited sandy lands.

Cross-sectional imaging: current status and future potential in adult celiac disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Clinical outcome is distinct between radiological stricture and endoscopic stricture in ileal Crohn's disease.

OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: • The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. • Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. • Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.

Preoperative computed tomography enterography-based radiomics signature: A potential predictor of postoperative anastomotic recurrence in patients with Crohn's disease.

BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.

Semi-Synthesis of Flavonoid Glycosides and Their Anti-Inflammatory and Antitumor Activities towards Triple Negative Breast Cancer.

BACKGROUND: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. OBJECTIVE: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti-inflammatory activities of these compounds. METHODS: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti-inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) production in LPS-induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, 1 H-NMR, and 13 C-NMR, and their cytotoxicity on the human triple-negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. RESULTS: Most of the compounds markedly reduced NO production in LPS-stimulated murine macrophages at the tested concentrations in a dose-dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti-inflammatory activities against NO production in LPS-induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF-α and IL-6 in a concentration-dependent manner. Most of the tested compounds showed remarkable anti-human TNBC activities. Compounds 1b-1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC50 values were all below 16.61 µM. In addition, compound 1l was the most cytotoxic with IC50 values of 1.38±0.31 µM, while the other compounds were inactive with inhibition rates <50 % at the highest concentration tested (20 µM). CONCLUSIONS: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS-stimulated murine macrophages at concentrations of 15 to 60 µM, and the inhibition generally increased in a dose-dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.

Cytotoxic nortriterpenoids from the barks of Juglans cathayensis.

A chemical study of 90% ethanol extract of the barks of Juglans cathayensis resulted in the isolation of three new nortriterpenoids, jugcathenoids A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated nortriterpenoids were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 50 µM.

Inflammatory bowel disease cross-sectional imaging: What's new?

Cross-sectional imaging-ultrasonography, computed tomography enterography, and magnetic resonance enterography-is a routine and indispensable tool for patients with Crohn's disease (CD) that helps to detect or monitor disease characteristics before, during, and after CD treatment. New emerging radiological technologies may have further clinical applications in the management of CD. In this review article, we focus on the latest developments in cross-sectional imaging in CD research, including its role in intra- and extra-luminal lesion detection, intestinal inflammation and fibrosis grading, therapeutic response assessment and outcome prediction, postoperative recurrence detection and prediction, and the gut-brain axis.

[Responses of intraspecific and interspecific variations of plant functional traits to grazing in degraded grassland]. / é€€åŒ–è‰åœ°ç‰©ç§ç§å† å’Œç§é—´åŠŸèƒ½æ€§çŠ¶å˜å¼‚å¯¹æ”¾ç‰§çš„å“åº”.

Understanding the responses of functional trait variation for grassland plants to grazing disturbance is highly helpful to clarify the community assembly mechanism, functional diversity maintenance, plant adaptation and their strategies. We investigated plant functional traits (plant height, root length, leaf area, root area, leaf dry matter content, shoot dry matter content, root dry matter content, specific leaf area, specific root length and root/ shoot ratio) and the responses of their variation characteristics to grazing disturbance in enclosure and grazing grasslands in Horqin Sandy Land. The results showed that the interspecific variation of functional trait was obviously higher than the intraspecific variation in degraded grassland. The relative contribution of interspecific variation to the overall trait variation ranged from 70.2% to 95.1%, while that of intraspecific variation only contributed 4.9% to 29.8%. However, that did not imply the intraspecific variation could be ignored in the community assembly. The interspecific variation in grazing grassland was lower than that in enclosed grassland, while the intraspecific variation increased but the interspecific variation decreased in grazing grassland. Grazing resulted in the decrease of leaf area and leaf dry matter content but the increase of specific root length for pastoral-resistant grasses. However, pastoral-tolerant forbs would improve their dominance in the community by decreasing specific root length and increa-sing leaf area and leaf dry matter content. The traits sensitive to grazing were leaf area, leaf dry matter content, specific root length, and specific leaf area. Leaf traits and root traits were significantly positively correlated within and with each other. Grazing would enhance the synergy of root traits while reduce the synergy of leaf traits. That meant grazing could change the trade-off strategy of functional traits in individual and population levels, and thus affect vegetation structure and function in community level.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn's Disease: A Pilot Study.

BACKGROUND: Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn's disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. METHODS: Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. RESULTS: Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P < .001, P < .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3 ± 8.7 kPa vs 15.3 ± 4.7 kPa; P = .022) and bowel wall thickness (8.5 ± 2.3 mm vs 6.9 ± 1.5 mm; P = .027) in the nonresponse group were significantly higher than in the response group. CONCLUSIONS: This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as 2 weeks after anti-tumor necrosis factor therapy in patients with Crohn's disease. Bowel ultrasound together with elasticity imaging could predict early response to anti-tumor necrosis factor therapy.

A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn's Disease.

Fibrostenosis is a serious complication of Crohn's disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T 1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T 1 relaxation time (T 1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson's trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T 1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p < 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.

[Effects of simvastatin on pulmonary fibrosis and endothelial - mesenchymal transition in the pulmonary fibrosis tissue of rats].

Objective: To investigate the effects of simvastatin (SIM) on pulmonary fibrosis and the expression of VE-cadherin(VE-cad),vimentin(VIM) and alpha-smooth muscle actin(α-SMA)in the pulmonary fibrosis tissue of rats. Methods: Sixty healthy male SD rats were randomly divided into control group(group A), bleomycin group(group B), 5 mg SIM group (group C) and 10 mg SIM group (group D),15 rats in each group. The model of rat pulmonary fibrosis was established by itraperitoneal injection of bleomycin(5 mg/kg). Since the first day of modeling, the rats of group C and D were treated with simvastatin suspension 5 mg/(kg·d) and 10 mg/(kg·d) by intragastric administration everyday, and the rats of group A and B were treated with equal volume of saline 10 ml/(kg·d) everyday. Five rats of each group were sacrificed randomly at the 7th, 14th and 28th day. Masson staining was used to observe the morphological changes of lung tissue in rats. The degree of fibrosis in lung tissues of each group was evaluated by the content of hydroxyproline (HYP) . The microvessel density (MVD) was analyzed by immunohistochemistry,The expressions of protein and mRNA of VE-cad, VIM and α-SMA were determined by immunohistochemistry and RT-PCR. Results: ①Compared with group A, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in lung tissues of groups B, C and D were increased significantly at the 7th, 14th and 28th day(all P＜0.05), which reached highest level at the 28th day. However, the mRNA and protein expression levels of VE-CAD were decreased significantly at the corresponding time (P＜0.05), which reached lowest level at 28th day. ②Compared with group B, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in groups C and D were decreased at the 7th, 14th and 28th day (all P＜0.05), which were decreased more obviously in group D at the 28th day. However, the mRNA and protein expression levels of VE-CAD were increased at the corresponding time (all P＜0.05), which were increased more obviously in group D at the 28th day. Conclusion: Simvastatin can reduce the degree of pulmonary fibrosis in rats through inhibiting the process of EnMT, which can enhance the expression of VE-cad and reduce the expression of VIM and α-SMA.

Hepatic mosaic enhancement pattern correlates with increased inflammatory activity and adverse therapeutic outcomes in patients with Crohn's disease.

PURPOSE: This study aimed to evaluate the role of hepatic mosaic enhancement pattern (HMEP) on computed tomography images in the disease activity and therapeutic outcome of Crohn's Disease (CD). METHODS: Twenty-five CD patients with HMEP comprised the HMEP group, and 25 CD patients without HMEP, who had a similar onset age, sex, and disease course with those in the HMEP group, comprised the non-HMEP group. No underlying liver/biliary disease was observed in any of the patients. Clinical characteristics, laboratory test results, Lémann index, and CD endoscopic index of severity (CDEIS) were compared between the groups using the Student t-, Mann-Whitney U, Chi square, or Fisher's exact tests. Patients received top-down, step-up, or traditional treatment during the follow-up period. After the 1-year follow-up, therapeutic outcomes (active inflammation [CDEIS > 3.5 if the endoscopic data were available, or C-reactive protein level > 5 mg/L if the endoscopic data were unavailable] or remission) were evaluated. RESULTS: The occurrence rate of fistulas/abscesses was higher in the HMEP group (84%, 21/25) than in the non-HMEP group (48%, 12/25) with no statistical significance (P = 0.056). The HMEP group showed a higher C-reactive protein level (P = 0.001), erythrocyte sedimentation rate (P = 0.013), and blood platelet count (P = 0.005). There was no significant difference in therapeutic strategies between the groups (P = 0.509). The HMEP group showed a significantly lower remission ratio after anti-inflammatory treatment than the non-HMEP group (P = 0.045). CONCLUSIONS: HMEP was correlated with increased inflammatory activity and adverse therapeutic outcomes in CD. This finding provided insights regarding novel markers of CD diagnosis and treatment.

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

BACKGROUND AND AIMS: Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. METHODS: MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. RESULTS: In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. CONCLUSIONS: MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

A novel identification system combining diffusion kurtosis imaging with conventional magnetic resonance imaging to assess intestinal strictures in patients with Crohn's disease.

PURPOSE: To determine the utility of diffusion kurtosis imaging (DKI) for assessing bowel fibrosis and to establish a new magnetic resonance imaging (MRI)-based classification based on DKI and conventional MRI parameters for characterizing intestinal strictures in Crohn's disease (CD) using the histological evaluation of resected intestine samples as the reference standard. METHODS: Thirty-one patients with CD undergoing preoperative conventional MRI and diffusion-weighted imaging (DWI) (b values = 0-2000 s/mm2) were consecutively enrolled. We classified the mural T2-weighted signal intensity and arterial-phase enhancement patterns on conventional MRI. We also measured DWI-derived apparent diffusion coefficients (ADCs) and DKI-derived apparent diffusion for non-Gaussian distribution (Dapp) and apparent diffusional kurtosis (Kapp). A new MRI-based classification was established to characterize intestinal strictures in CD. Its performance was validated in nine additional patients with CD. RESULTS: Histological inflammation grades were significantly correlated to T2-weighted signal intensity (r = 0.477; P < 0.001) and ADC (r = - 0.226; P = 0.044). Histological fibrosis grades were moderately correlated to Kapp (r = 0.604, P < 0.001); they were also correlated to Dapp (r = - 0.491; P < 0.001) and ADC (r = - 0.270; P = 0.015). T2-weighted signal intensity could differentiate between no-to-mild and moderate-to-severe bowel inflammation (sensitivity, 0.970; specificity, 0.479). Kapp could differentiate between no-to-mild and moderate-to-severe bowel fibrosis (sensitivity, 0.959; specificity, 0.781). The agreement between the new MRI-based classification and the histological classification was moderate in the test (κ = 0.507; P < 0.001) and validation (κ = 0.530; P < 0.001) sets. CONCLUSIONS: DKI can be used to assess bowel fibrosis. The new MRI-based classification can help to distinguish between fibrotic and inflammatory intestinal strictures in patients with CD.

Cross-sectional imaging for assessing intestinal fibrosis in Crohn's disease.

More than 30% of patients with Crohn's disease (CD) develop fibrotic strictures in the bowel as the disease progresses. Excessive deposition of extracellular matrix components in the submucosa and smooth muscle hypertrophy or hyperplasia are the main features of fibrosis in CD. Cross-sectional imaging technology provides a wealth of information on the anatomy, histological composition, and physiological function of the bowel, allowing for a non-invasive and complete evaluation of associated abnormalities. This review summarizes recent advances in and the potential technologies of cross-sectional imaging for assessing intestinal fibrosis in CD, including ultrasound imaging, computed tomography, and magnetic resonance imaging.

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93-26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30-2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14-4·42]; p<0·00001; I2=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22-5·48]; p=0·030; I2=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 [95% CI 1·17-7·48]; p=0·02; I2=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.

Magnetisation transfer imaging adds information to conventional MRIs to differentiate inflammatory from fibrotic components of small intestinal strictures in Crohn's disease.

OBJECTIVES: Identifying inflammation- or fibrosis-predominant strictures in Crohn's disease (CD) is crucial for treatment strategies. We evaluated the additive value of magnetisation transfer (MT) to conventional MRI for differentiating CD strictures using surgical histopathology as a reference standard. METHODS: Twenty-eight consecutive CD patients who underwent MRI preoperatively were recruited. MRI parameters included T2-weighted imaging (T2WI) hyperintensity, bowel wall thickness, enhancement pattern changes over time, enhancement pattern and gain ratio in dynamic contrast-enhanced phases, and MT ratio. Correlation analysis was performed using Spearman's rank test. Receiver operating characteristic curve analysis and Cohen's κ were used. A model with combined MRI variables characterising intestinal strictures was proposed and validated in 14 additional CD patients. RESULTS: Significant correlations with histological inflammation scores were shown for wall thickness (r = 0.361, p = 0.001) and T2WI hyperintensity (r = 0.396, p < 0.001), whereas histological fibrosis scores were significantly correlated with MT ratio (r = 0.681, p < 0.001) and wall thickness (r = 0.461, p < 0.001). T2WI hyperintensity could differentiate mild from moderate-to-severe inflammation with a sensitivity of 0.871 and a specificity of 0.800. MT ratio could discriminate mild from moderate-to-severe fibrosis with a sensitivity and a specificity of 0.913 and 0.923, respectively. Combining MT ratio and T2WI hyperintensity, the MRI classification moderately agreed with the pathological stricture classification (p < 0.01, κ = 0.549). In the validation set, the diagnostic accuracy of T2WI hyperintensity and MT ratio were 86% and 89%, with good agreement between MRI and histopathological classification (p < 0.01, κ = 0.665). CONCLUSIONS: MT ratio combined with conventional MRI improves the differentiation of fibrotic from inflammatory components of small-bowel strictures in CD patients. KEY POINTS: • MT ratio from magnetisation transfer imaging combined with T2WI from conventional MRI can simultaneously characterise bowel fibrosis and inflammation in adult Crohn's disease.

A novel collagen area fraction index to quantitatively assess bowel fibrosis in patients with Crohn's disease.

BACKGROUND: A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn's disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis. METHODS: We analyzed the histopathological data of 31 patients with Crohn's disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis. RESULTS: Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn's disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001). CONCLUSIONS: Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis.

Magnetic Graphene Oxide-Fe3O4-PANI Nanoparticle Adsorbed Platinum Drugs as Drug Delivery Systems for Cancer Therapy.

Graphene-based magnetic nanoparticles (NPs) were synthesized using a simple and effective chemical precipitation method. To determine the biocompatibility of GO-Fe3O4-PANI NPs with MTT assay, cytotoxicity testing from a low concentration (1 µg/mL) to a high concentration (125 µg/mL) was conducted using various cancer and normal cell lines. Cytotoxicity testing for cancer cell lines (SMMC-7721, HepG-2, RAW264.7) and normal cell lines (HL-7702) showed almost no toxicity within the 1~125 µg/mL concentration range. Carboplatin (CBP) and oxaliplatin (OXP) were then used as drug models to study the drug release of CBP and OXP loaded on GO-Fe3O4-PANI NPs in vitro. Results indicated that the release of CBP and OXP from GO-Fe3O4-PANI NPs were affected by pH, dose, and temperature. The release of CBP was more sensitive to pH, and the amounts released in neutral and acidic environments (pH 6.0 and 7.4, respectively) were higher than those released in alkaline environments (pH 8.0). Meanwhile, at different pH levels, the release of OXP was not as large. In addition, at a low temperature (27 °C), the amount released is small when the energy level does not meet that required by C═N. At a considerably higher temperature (47 °C), the energy required for C═N fracture is met, allowing the slow release of the drug over a longer period. The results of our studies suggest that GO-Fe3O4-PANI NPs are biocompatible with MTT assay, and as drug delivery systems, these particular NPs can lead to advances in cancer treatment.