Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study.

Background/Aims: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. Methods: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. Results: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. Conclusions: In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Early proactive monitoring of DNA-thioguanine in patients with Crohn's disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers.

BACKGROUND: Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines. Dose optimization guided by nudix hydrolase 15 (NUDT15) has significantly reduced the early leucopenia rate, but there are no definitive biomarkers for late risk leucopenia prediction. AIM: To determine the predictive value of early monitoring of DNA-thioguanine (DNATG) or 6-thioguanine nucleotides (6TGN) for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn's disease (CD). METHODS: Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations. Late leucopenia was defined as a leukocyte count < 3.5 × 109/L over two months. RESULTS: Of 148 patients studied, late leucopenia was observed in 15.6% (17/109) of NUDT15/thiopurine methyltransferase (TPMT) normal and 64.1% (25/39) of intermediate metabolizers. In patients suffering late leucopenia, early DNATG levels were significantly higher than in those who did not develop late leucopenia (P = 4.9 × 10-13). The DNATG threshold of 319.43 fmol/µg DNA could predict late leucopenia in the entire sample with an area under the curve (AUC) of 0.855 (sensitivity 83%, specificity 81%), and in NUDT15/TPMT normal metabolizers, the predictive performance of a threshold of 315.72 fmol/µg DNA was much more remarkable with an AUC of 0.902 (sensitivity 88%, specificity 85%). 6TGN had a relatively poor correlation with late leucopenia whether in the entire sample (P = 0.021) or NUDT15/TPMT normal or intermediate metabolizers (P = 0.018, P = 0.55, respectively). CONCLUSION: Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD, especially the former.

Family farming in climate change: Strategies for resilient and sustainable food systems.

Family farming plays a pivotal role in ensuring household food security and bolstering the resilience of food systems against climate change. Traditional agricultural practices are evolving into context-specific, climate-resilient systems such as family farming, homestead gardening, and urban agriculture. This study examines the ways in which family farming can foster climate-resilient food systems amidst climate vulnerabilities. A systematic literature review spanning the past 22 years was undertaken to develop a conceptual framework. From this review, 37 pertinent documents were identified, leading to the creation of a context-specific, climate-resilient food system framework. The research posits that family farming facilitates easy access to food and nutrition by capitalizing on family-sourced land, labor, and capital, and by securing access to technology and markets. Each facet of family farming is intricately linked with sustainability principles. Local adaptation strategies employed by climate-vulnerable households can diminish their vulnerability and augment their adaptive, absorptive, and transformative capacities, enabling them to establish a climate-resilient food system. The research further reveals that farming families employ a myriad of strategies to fortify their food systems. These include crop diversification, adjusting planting times, cultivating high-value crops and fish, planting fruit trees, rearing poultry and livestock, and leveraging their land, labor, and resources-including their homesteads-to access food and nutrition. This study endorses the climate-resilient family farming framework and offers multiple metrics for assessing the resilience of family farming in developing countries.

A novel location classification system for Crohn's disease based on small bowel involvement: a better predictor of disease progression.

Background: Small bowel involvement is related to poor prognosis in Crohn's disease (CD), which may be a potential marker to stratify patients with a high risk of progression. This study aimed to establish a novel location classification system for CD and to develop a predictive model for disease progression. Methods: Consecutive patients with non-stricturing/non-penetrating CD were retrospectively included in the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou, P. R. China) between January 2012 and January 2018. Patients were classified into two groups according to disease location: small bowel involvement group and isolated colon group. The primary outcome was disease progression to stricturing or penetrating phenotypes. Progression-free survival was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Results: A total of 463 patients were analysed, with a median follow-up time of 55.3 months. Patients with small bowel involvement had a higher risk of disease progression than those with isolated colon disease (hazard ratio = 1.998, P = 0.007), while no differences were found between Montreal location classification and disease progression. Median progression-free survival was higher in the isolated colon group than in the small bowel involvement group (84.5 vs 77.3 months, P = 0.006). Four independent factors associated with disease progression were identified: small bowel involvement, duration of onset of >1 year, deep mucosal ulcer, and C-reactive protein levels of ≥10 mg/L (all P < 0.05). The nomogram model based on these factors showed good performance in predicting disease progression, with a C-index of 0.746 (95% confidence interval, 0.707-0.785). Conclusions: Classifying CD based on small bowel involvement and isolated colon was superior to the Montreal location classification for predicting disease progression.

Should I speak up? How trust in leaders and leader-leader exchanges influence nurses' voice behaviour.

AIM: Discussing the nurses' voice behaviour could support the managers in making the right decisions and solve problems. DESIGN: This was a discursive paper. METHODS: The discursive was based on reviewing the literature. RESULTS: Nurses play a critical role in offering useful constructive advice, which leads to management figuring out and solving problems immediately for the purpose of bettering the working environment. Therefore, we assert that trust in leadership and the leader-leader exchange system also plays a critical role in enforcing voice behaviour. Trust is a crucial aspect of voice behaviour, and integrated trust in leadership and leader-leader exchange as a possible practical suggestion for the fostering of voice behaviour are proposed. Nurse managers must maintain a sense of reciprocal moral obligation in order to nurture value-driven voice behaviour. It is important that open dialogue, active listening and trust in leadership exist. Nurse managers must consider ways to foster mutual trust, and support and enable nurses to use voice behaviour in everyday practice.

Single or continuous multiple intravenous re-induction in Crohn's disease patients who lost response to ustekinumab: Evidence from real-world data.

BACKGROUND AND AIMS: Re-induction optimization of ustekinumab is effective in Crohn's disease (CD) patients who experienced a loss of response (LOR) to ustekinumab. However, whether continuous multiple intravenous optimization is better than single dose re-induction remains unknown. We aimed to compare effectiveness of two strategies in CD patients with LOR to ustekinumab. METHODS: We retrospectively included CD patients who had LOR to standardized ustekinumab therapy. They were divided into three groups according to different times (one to three) for re-induction. RESULTS: This study included 50, 26 and 22 of 98 eligible patients in one intravenous re-induction subgroup, double intravenous re-induction subgroup and three intravenous re-induction subgroup, respectively. At week 24, 67.3%, 75.5%, 56.6%, 69.8% and 61.2% of all achieved steriod free clinical remission, clinical response, endoscopic remission, endoscopic response and C-reactive protein normalization, respectively. No differences were found in all endpoints between three groups. Ustekinumab trough level at week 24 but not times of re-induction showed a tendency to predict clinical remission. No serious adverse events were found in this cohort. CONCLUSION: Intravenous re-induction was safe and effective in CD patients who experienced LOR to ustekinumab. Trough level of ustekinumab but not times of intravenous re-induction may associated with clinical efficacy.

Amino acid-based enteral nutrition is effective for pediatric Crohn's disease: a multicenter prospective study.

Background: Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Methods: Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t-tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Results: Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P < 0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P < 0.05). There were no severe adverse effects. Conclusions: Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings.

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study.

Background: Ustekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort. Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

Exclusive Enteral Nutrition Orchestrates Immunological Balances as Early as Week 4 in Adult Patients of Crohn's Disease: A Pilot, Open-Lable Study.

BACKGROUND AND AIMS: The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn's disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. METHODS: This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. RESULTS: Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. CONCLUSIONS: EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.

Baseline and Postinduction Intestinal Ultrasound Findings Predict Long-term Transmural and Mucosal Healing in Patients With Crohn's Disease.

BACKGROUND: Intestinal ultrasound (IUS) is becoming a standard assessment tool in Crohn's disease (CD), but limited data exist on its ability to predict long-term objective outcomes. Therefore, we aimed to investigate the predictive value of IUS findings for long-term transmural healing (TH) and mucosal healing (MH) in CD. METHODS: We prospectively included consecutive CD patients with active endoscopic disease and bowel wall thickness (BWT) >3.0 mm, initiating infliximab. Intestinal ultrasound parameters (ie, BWT, inflammatory mesenteric fat [i-fat], bowel blood flow and stratification) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) were collected at baseline, after 14 to 26 weeks (visit 1, postinduction) and 44 to 56 weeks (visit 2). Transmural healing (normalization of all IUS parameters) and MH (SES-CD ≤2) were assessed at visit 2. RESULTS: One hundred twenty-nine patients were evaluated. At visit 2, 38.0% and 48.1% of patients achieved TH and MH, respectively. All the IUS parameters and IBUS-SAS showed improvement at visit 1 and visit 2 compared with the baseline (all P < .001). Multivariable analysis found that presence of i-fat at baseline (odds ratio [OR], 0.57; P = .008) and greater postinduction BWT (OR, 0.24; P < .001) were negative predictors for TH, while higher baseline (OR, 0.98; P = .013) and postinduction (OR, 0.94; P < .001) IBUS-SAS predicted negatively for MH. Postinduction BWT <4.5mm best predicted TH (AUC 0.85; P < .001), while postinduction IBUS-SAS <25.0 best predicted MH (AUC 0.82; P < .001). Moreover, colonic disease was associated with higher risk of TH (OR, 2.55; P = .027), and disease duration >24 months with lower risk of MH (OR, 0.27; P = .006). CONCLUSIONS: Baseline and postinduction IUS findings reliably predict long-term TH and MH in patients with CD receiving infliximab.

Baseline and postinduction intestinal ultrasound findings reliably predict long-term transmural and mucosal healing in patients with Crohn's disease receiving infliximab. International Bowel Ultrasound Segmental Activity Score is responsive to treatment.

Big data-driven public health policy making: Potential for the healthcare industry.

The use of healthcare data analytics is anticipated to play a significant role in future public health policy formulation. Therefore, this study examines how big data analytics (BDA) may be methodically incorporated into various phases of the health policy cycle for fact-based and precise health policy decision-making. So, this study explores the potential of BDA for accurate and rapid policy-making processes in the healthcare industry. A systematic review of literature spanning 22 years (from January 2001 to January 2023) has been conducted using the PRISMA approach to develop a conceptual framework. The study introduces the emerging topic of BDA in healthcare policy, goes over the advantages, presents a framework, advances instances from the literature, reveals difficulties and provides recommendations. This study argues that BDA has the ability to transform the conventional policy-making process into data-driven process, which helps to make accurate health policy decision. In addition, this study contends that BDA is applicable to the different stages of health policy cycle, namely policy identification, agenda setting as well as policy formulation, implementation and evaluation. Currently, descriptive, predictive and prescriptive analytics are used for public health policy decisions on data obtained from several common health-related big data sources like electronic health reports, public health records, patient and clinical data, and government and social networking sites. To effectively utilize all of the data, it is necessary to overcome the computational, algorithmic and technological obstacles that define today's extremely heterogeneous data landscape, as well as a variety of legal, normative, governance and policy limitations. Big data can only fulfill its full potential if data are made available and shared. This enables public health institutions and policymakers to evaluate the impact and risk of policy changes at the population level.

Comparison and development of machine learning for thalidomide-induced peripheral neuropathy prediction of refractory Crohn's disease in Chinese population.

BACKGROUND: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence. AIM: To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables. METHODS: A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score. RESULTS: The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [P = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, P = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 (P = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 (P = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 (P = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence. CONCLUSION: The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients.

Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.

The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.

Plasma lipidomic profiling of thiopurine-induced leukopenia after NUDT15 genotype-guided dosing in Chinese IBD patients.

Introduction: Thiopurines, azathiopurine (AZA) and mercaptopurine (6-MP) have been regularly used in the treatment of inflammatory bowel disease (IBD). Despite optimized dosage adjustment based on the NUDT15 genotypes, some patients still discontinue or change treatment regimens due to thiopurine-induced leukopenia. Methods: We proposed a prospective observational study of lipidomics to reveal the lipids perturbations associated with thiopurine-induced leukopenia. One hundred and twenty-seven IBD participants treated with thiopurine were enrolled, twenty-seven of which have developed thiopurine-induced leucopenia. Plasma lipid profiles were measured using Ultra-High-Performance Liquid Chromatography-Tandem Q-Exactive. Lipidomic alterations were validated with an independent validation cohort (leukopenia n = 26, non-leukopenia n = 74). Results: Using univariate and multivariate analysis, there were 16 lipid species from four lipid classes, triglyceride (n = 11), sphingomyelin (n = 1), phosphatidylcholine (n = 1) and lactosylceramide (n = 3) identified. Based on machine learning feature reduction and variable screening strategies, the random forest algorithm established by six lipids showed an excellent performance to distinguish the leukopenia group from the normal group, with a model accuracy of 95.28% (discovery cohort), 79.00% (validation cohort) and an area under the receiver operating characteristic (ROC) curve (ROC-AUC) of 0.9989 (discovery cohort), 0.8098 (validation cohort). Discussion: Our novel findings suggested that lipidomic provided unique insights into formulating individualized medication strategies for thiopurines in IBD patients.

Neutrophil-to-lymphocyte ratio for predicting postoperative recurrence in Crohn's disease patients with isolated anastomotic lesions.

Background: Patients with isolated anastomotic lesions (iAL) are common in postoperative Crohn's disease (CD) and have heterogeneous prognosis. Objectives: To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in CD patients with iAL. Design: A bicenter retrospective cohort study. Methods: CD patients who received ileocolonic resection from 2013 and 2020 and had a modified Rutgeerts score of i2a were recruited. NLR was determined within 1 week around the initial endoscopy after ileocolectomy. The primary outcome was clinical recurrence. Kaplan-Meier method and Cox hazard regression analysis were utilized to assess the association between candidate variables and outcomes of interest. Results: In total, 411 postoperative CD patients were preliminarily reviewed and 83 patients were eligible. In total, 36 (48.6%) patients experienced clinical recurrence with a median follow-up time of 16.3 (interquartile range, 9.7-26.3) months. NLR > 2.45 and age at surgery >45 years had higher cumulative incidence of clinical recurrence in the Kaplan-Meier analysis. After adjusted for potential confounders, NLR > 2.45 was the only independent risk factor for clinical recurrence, with an adjusted hazard ratio (HR) of 2.88 [95% confidence interval (CI), 1.39-6.00; p = 0.005]. Furthermore, a risk score based on NLR and age at surgery were built to further stratify patients. Compared to those who scored 0, patients with a score of 1 and 2 had an adjusted HR of 2.48 (95% CI, 1.22-5.02) and 6.97 (95% CI, 2.19-22.16) for developing clinical recurrence, respectively. Conclusions: NLR is a promising prognostic biomarker for CD patients with iAL. The utilization of NLR and the risk score to stratify patients may facilitate the personalized management in patients with iAL.

Integrated Multi-omics Approach Reveals the Interaction of Brain-gut in D-galactose-induced Aging Model Mice / 中国生物化学与分子生物学报

Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.

Cloning and expression analysis of JrGI gene in walnut / 生物工程学报

GI (GIGANTEA) is one of the output key genes for circadian clock in the plant. The JrGI gene was cloned and its expression in different tissues was analyzed to facilitate the functional research of JrGI. RT-PCR (reverse transcription-polymerase chain reaction) was used to clone JrGI gene in present study. This gene was then analyzed by bioinformatics, subcellular localization and gene expression. The coding sequence (CDS) full length of JrGI gene was 3 516 bp, encoding 1 171 amino acids with a molecular mass of 128.60 kDa and a theoretical isoelectric point of 6.13. It was a hydrophilic protein. Phylogenetic analysis showed that JrGI of 'Xinxin 2' was highly homologous to GI of Populus euphratica. The result of subcellular localization showed that JrGI protein was located in nucleus. The JrGI, JrCO and JrFT genes in female flower buds undifferentiated and early differentiated of 'Xinxin 2' were analyzed by RT-qPCR (real-time quantitative PCR). The results showed that the expression of JrGI, JrCO and JrFT genes were the highest on morphological differentiation, implying the temporal and special regulation of JrGI in the differential process of female flower buds of'Xinxin 2'. In addition, RT-qPCR analysis showed that JrGI gene was expressed in all tissues examined, whereas the expression level in leaves was the highest. It is suggested that JrGI gene plays a key role in the development of walnut leaves.

Mechanism of Proliferation and Apoptosis of Acute Promyelocytic Leukemia Cell Line NB4 Induced by TPA / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism.@*METHODS@#The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT.@*RESULTS@#Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells.@*CONCLUSION@#TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.

Lipidomics reveals significant alterations associated with exclusive enteral nutrition treatment in adult patients with active Crohn's disease.

Background: Crohn's disease (CD), a type of inflammatory bowel disease, is a chronic idiopathic disorder of the gastrointestinal tract with an increasing global incidence. Exclusive enteral nutrition (EEN) is a diet therapy that is effective in the management of active CD with unknown etiology. Lipid metabolism plays an important role in CD and may be associated with EEN treatment. This study compared the plasma lipid profiles before and after EEN in adults with active CD to those of healthy controls (HCs). Methods: Eleven adult patients with active CD who received enteral nutrition formula treatment for 12 weeks were included, along with 17 HCs. The profiles of 869 plasma lipid species were measured, and inflammatory and nutrition-associated indices were evaluated in the patients. Results: Nine patients achieved clinical remission following 12 weeks of EEN treatment, and four achieved mucosal healing. Before EEN, 80 lipid species and 17 lipid classes were significantly different between patients with CD and HCs. After EEN treatment, 103 lipid species and 12 lipid classes were significantly different between patients with CD and HCs. Significant changes in 7 lipid classes and 38 lipid species were observed between the pre- vs. post-treatment CD patients. The levels of simplified glucosylceramide series, monogalactosyldiacylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylcholine increased, while those of phosphatidylglycerol and phosphatidylinositol diphosphate decreased significantly after EEN. These lipid classes and species were associated with the inflammatory and nutritional indices. Pathway analysis suggested the metabolism of arachidonic acid, glycerophospholipids, linoleate, and phosphatidylinositol phosphate was related to the EEN mechanism. Conclusions: EEN induces alterations in multiple lipid classes and species, leading to clinical improvements. Lipid metabolism may be involved in the EEN anti-inflammatory effect.