Analysis and purification of innate lymphoid cells in human intestine and blood by flow cytometry.

The role of innate lymphoid cells (ILCs)-including natural killer cells, helper-like ILC1s, ILC2s, ILC3s, and lymphoid tissue inducers-in human cancer is still poorly understood due to the scarcity of cell number. To address this, we present a protocol to analyze or purify ILCs from human blood, adjacent intestine, and colorectal tumor tissue. We describe steps for tissue and blood treatment, density centrifugation, antibody staining, and cell sorting. For complete details on the use and execution of this protocol, please refer to Qi et al. (2021).1.

Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease.

Emerging evidence indicates that a vicious cycle between inflammation and microthrombosis catalyzes the pathogenesis of inflammatory bowel disease (IBD). Over-stimulated inflammation triggers a coagulation cascade and leads to microthrombosis, which further complicates the injury through tissue hypoxia and ischemia. Herein, an injectable protein hydrogel with anti-thrombosis and anti-inflammation competency is developed to impede this cycle, cross-linked by silver ion mediated metal-ligand coordination and electronic interaction with sulfhydryl functionalized bovine serum albumin and heparin, respectively. The ex vivo experiments show that the hydrogel, HEP-Ag-BSA, exhibits excellent self-healing ability, injectability, biocompatibility, and sustained drug release. HEP-Ag-BSA also demonstrates anti-coagulation and anti-inflammation abilities via coagulation analysis and lipopolysaccharide stimulation assay. The in vivo imaging confirms the longer retention time of HEP-Ag-BSA at inflammatory sites than in normal mucosa owing to electrostatic interactions. The in vivo study applying a mouse model with colitis also reveals that HEP-Ag-BSA can robustly inhibit inflammatory microthrombosis with reduced bleeding risk. This versatile protein hydrogel platform can definitively hinder the "inflammation and microthrombosis" cycle, providing a novel integrated approach against IBD.

Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer.

Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP+ fibroblasts and SPP1+ macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-ß, and interleukin-1, which would stimulate the formation of immune-excluded desmoplasic structure and limit the T cell infiltration. Furthermore, we find patients with high FAP or SPP1 expression achieved less therapeutic benefit from an anti-PD-L1 therapy cohort. Our results provide a potential therapeutic strategy by disrupting FAP+ fibroblasts and SPP1+ macrophages interaction to improve immunotherapy.

Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer.

Objective: Epithelial-to-mesenchymal transition (EMT) is tightly associated with the invasion and metastasis of pancreatic cancer with rapid progression and poor prognosis. Notably, gene alternative splicing (AS) event plays a critical role in regulating the progression of pancreatic cancer. Therefore, this study aims to identify the EMT-related AS event in pancreatic cancer. Methods: The EMT-related gene sets, transcriptomes, and matched clinical data were obtained from the MSigDB, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Key gene AS events associated with liver metastasis were identified by prognostic analysis, gene set variation analysis (GSVA), and correlation analysis in pancreatic cancer. The cell line and organoid model was constructed to evaluate these key gene AS events in regulating pancreatic cancer in vitro. Furthermore, we established an EMT-related gene set consisting of 13 genes by prognostic analysis, the role of which was validated in two other databases. Finally, the human pancreatic cancer tissue and organoid model was used to evaluate the correlation between the enrichment of this gene set and liver metastasis. Results: Prognostic analysis and correlation analysis revealed that eight AS events were closely associated with the prognosis of pancreatic cancer. Furthermore, the expression of TMC7 and CHECK1 AS events was increased in the metastatic lesions of the human tissue and organoid model. Additionally, the knockdown of exon 17 of TMC7 significantly inhibited the proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments. Finally, the expression of exon 17 of TMC17 exhibited a significant correlation with the poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Conclusion: The AS events of TMC7 and CHECK1 were associated with liver metastasis in pancreatic cancer. Moreover, exon 17 of TMC7 could be a potential therapeutic target in pancreatic cancer.

Prevalence of Sarcopenia and Its Effect on Postoperative Complications in Patients with Crohn's Disease.

BACKGROUND AND AIMS: Sarcopenia is a prognostic factor of outcomes for various diseases, but reports on sarcopenia in patients with Crohn's disease (CD) are few. We aim to determine the prevalence of sarcopenia and assess the role of sarcopenia in postoperative complications in patients with CD at a tertiary referral center. METHODS: Patients who underwent intestinal surgery for CD from January 2013 to October 2019 were retrospectively enrolled. The L3 skeletal muscle mass index (SMI) was used to identify sarcopenia. Demographic data, preoperative laboratory data, surgical details, and hospital outcomes were recorded. The factors associated with postoperative complications were evaluated through univariate and multivariate analyses. RESULTS: One hundred and twenty-four patients were enrolled. Thirty-four of them (27.4%), including 11 males, were diagnosed with sarcopenia. Compared with patients without sarcopenia, sarcopenic patients had a significantly lower BMI (P < 0.001); lower preoperative serum albumin (P = 0.006), prealbumin (P = 0.030), and hemoglobin levels (P < 0.001); longer hospital stay (34.4 ± 26.8 days vs. 22.8 ± 15.6 days, P = 0.003); and more occurrences of complications (41.2% vs. 23.3%, P = 0.049). The overall incidence of postoperative complications was 28.2%. Infection (51.4%) and intestinal fistula (22.9%) were the most common among such complications. Through the multivariate analysis, sarcopenia was identified as an independent risk factor for major postoperative complications (odds ratio = 3.974, 95%CI = 1.171-13.489, P = 0.027). CONCLUSION: Sarcopenia is common in patients with CD requiring bowel resection, and it significantly increases the risk of major postoperative complications.

Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression.

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes differing from conventional T lymphocytes in having no antigen-specific receptors. ILCs include natural killer (NK) cells, helper-like ILC1s, ILC2s, and ILC3s, and lymphoid tissue-inducer (LTi) cells. Tumor ILCs are frequently found in various cancers, but their roles in cancer immunity and immunotherapy remain largely unclear. We report here the single-cell characterization of blood and gut helper-like ILC subsets in healthy conditions and in colorectal cancer (CRC). The healthy gut contains ILC1s, ILC3s, and ILC3/NKs, but no ILC2s. Additional tumor-specific ILC1-like and ILC2 subsets were identified in CRC patients. Signaling lymphocytic activation molecule family member 1 (SLAMF1) was found to be selectively expressed on tumor-specific ILCs, and higher levels of SLAMF1+ ILCs were observed in the blood of CRC patients. The SLAMF1-high group of CRC patients had a significantly higher survival rate than the SLAMF1-low group, suggesting that SLAMF1 is an anti-tumor biomarker in CRC.

Circulating miR-221/222 reduces CD4+ T cells by inhibiting CD4 expression in colorectal cancer.

Many patients with cancers have low levels of CD4+ in their peripheral blood. However, the molecular mechanism is still unclear. Here, we found that the blood levels of miR-221 and miR-222 were dramatically increased in patients with colorectal cancer (CRC), and both circulating miR-211 and miR-222 served as sensitive diagnostic markers with an area under the curve of 0.8790 and 0.9148, respectively. Transfection of either miR-221 or miR-222 resulted in the reduction of the surface CD4 antigen level but not the surface CD8 antigen level. The luciferase reporter assay showed that miR-221/222 directly regulated CD4 expression in human primary T cells. These data showed that miR-221/222 levels were upregulated in the blood of patients with CRC and that the expression of CD4 in human primary T cells was inhibited by miR-221/222. These findings provide a novel strategy for modulating the number of CD4+ T cells in the blood and further adjusting the microenvironment suitable for immunotherapy.

Colon-Targeted Adhesive Hydrogel Microsphere for Regulation of Gut Immunity and Flora.

Intestinal immune homeostasis and microbiome structure play a critical role in the pathogenesis and progress of inflammatory bowel disease (IBD), whereas IBD treatment remains a challenge as the first-line drugs show limited therapeutic efficiency and great side effect. In this study, a colon-targeted adhesive core-shell hydrogel microsphere is designed and fabricated by the ingenious combination of advanced gas-shearing technology and ionic diffusion method, which can congregate on colon tissue regulating the gut immune-microbiota microenvironment in IBD treatment. The degradation experiment indicates the anti-acid and colon-targeted property of the alginate hydrogel shell, and the in vivo imaging shows the mucoadhesive ability of the thiolated-hyaluronic acid hydrogel core of the microsphere, which reduces the systematic exposure and prolongs the local drug dwell time. In addition, both in vitro and in vivo study demonstrate that the microsphere significantly reduces the secretion of pro-inflammatory cytokines, induces specific type 2 macrophage differentiation, and remarkably alleviates colitis in the mice model. Moreover, 16S ribosomal RNA sequencing reveals an optimized gut flora composition, probiotics including Bifidobacterium and Lactobacillus significantly augment, while the detrimental communities are inhibited, which benefits the intestinal homeostasis. This finding provides an ideal clinical candidate for IBD treatment.

Second-line sunitinib for Chinese patients with advanced gastrointestinal stromal tumor: 37.5 mg schedule outperformed 50 mg schedule in adherence and prognosis.

BACKGROUND: Sunitinib is widely accepted as a second-line treatment for advanced gastrointestinal stromal tumor (GIST). This study aimed to evaluate patients' adherence to sunitinib treatment and optimize the dosing schedule for Chinese patients. METHODS: The present study analyzed medical data of patients with advanced GIST treated in Shanghai Ruijin Hospital and Shaoxin Shangyu People's Hospital. Adherence to sunitinib was evaluated through questionnaires. Treatment outcomes were evaluated during follow-up. RESULTS: Medical data of 107 patients were included in the analysis. The overall progression free survival (PFS) was 41 weeks (95% CI: 39.0-43.0 weeks), and overall survival (OS) was 70 weeks (95% CI: 68.1-71.9 weeks). Sixty-five patients completed the questionnaire evaluation of sunitinib adherence. Patients with good adherence had longer PFS than patients with poor adherence (P=0.032). Patients following the 37.5 mg continuous daily dosage (CDD) schedule had significantly longer PFS and OS than those following the 50 mg "4-week on 2-week off" schedule (50 mg 4/2 schedule), (P=0.044, and 0.016 respectively). Meanwhile, 64.1% of patients following the 50 mg 4/2 schedule suffered severe treatment toxicity Grade 2-3, and this percentage was significantly higher than that of patients following the 37.5 mg CDD schedule (P=0.010). The 50 mg 4/2 schedule and severe treatment toxicity were independent risk factors related to poor adherence (P=0.039, and 0.006 respectively). CONCLUSIONS: Sunitinib 37.5 mg CDD schedule was related to improved adherence and prognosis compared with 50 mg 4/2 schedule. Sunitinib 37.5 mg CDD schedule might be a more suitable dosage schedule in Chinese patients with advanced GIST after imatinib failure.

Chromogranin A: A Valuable Serum Diagnostic Marker for Non-Insulinoma Neuroendocrine Tumors of the Pancreas in a Chinese Population.

BACKGROUND Pancreatic neuroendocrine tumors (P-NETs) are uncommon neoplasms, with few studies to date assessing serum biomarkers for the diagnosis of P-NETs. This study assessed the ability of serum chromogranin A (CgA) concentrations to distinguish P-NETs from other pancreatic lesions in a Chinese population and to determine the histological grades of P-NETs. MATERIAL AND METHODS This prospective study enrolled 165 patients, including 73 with proven P-NETs, 60 with malignant tumors of the pancreas, and 32 with benign lesions of the pancreas. Serum CgA concentrations were measured by ELISA. RESULTS Serum CgA concentrations were significantly higher in patients with P-NET than in patients with other pancreatic malignancies and benign lesions (P<0.001), but did not differ significantly in the latter 2 groups (P=0.827). Serum CgA concentrations were significantly higher in patients with non-insulinoma P-NETs than in the other groups (P<0.001), but did not differ significantly in patients with insulinoma and patients with non-P-NETs (P=0.668). Receiver operating characteristic (ROC) curves revealed that a serum CgA concentration of 77.8 ng/ml could distinguish patients with non-insulinoma P-NETs from patients with non-P-NETs, with a sensitivity of 96.7%, a specificity of 76.1%, and an area under the ROC curve of 0.897. In patients with P-NETs, multifactor analysis showed that the non-insulinoma subtype and the presence of liver metastases were associated with elevated serum CgA (both p<0.001). CONCLUSIONS Serum CgA concentration may be a valuable diagnostic biomarker for non-insulinoma P-NETs. Elevated serum CgA is likely associated with liver metastases.

Dynamics of the Salivary Microbiome During Different Phases of Crohn's Disease.

Crohn's disease is a chronic disorder that typically affects the gastrointestinal tract. The increased incidence in the recent years, especially in Asian countries, prompts for performing studies and gain newer insights into the etiology and pathogenesis of the disease. Among other causative factors, gut microbiome and its cross-talk with the salivary microbiome is a known factor that has a plausible role in the pathogenesis of Crohn's disease. The gut microbiome has been extensively studied, however, the salivary microbiome and its dynamics during different phases of this disease remain understudied. In this study, we obtained saliva samples from the patients during active and remission phases of the disease and compared them with control samples and highlighted the differences in taxonomic as well as predicted functional pathways among them. Our results indicated that the α and ß diversities were significantly lower during the active phase in contrast with remission phase and healthy samples. In general, Firmicutes were most abundant among the three sample groups, followed by Bacteroidetes and Proteobacteria. Genus level distribution highlighted Streptococcus, Neisseria, Prevotella, Haemophilus, and Veillonella as the five most abundant taxa. Differential abundance analysis of the three sample groups identified significant enrichment of 30 bacterial taxa in the active phase that included g_Prevotella, f_Prevotellaceae, and p_Bacteroidetes. Furthermore, remission phase and control also exhibited significant enrichment of 24 and 22 bacterial taxa, respectively. Eleven differentially abundant pathways were also identified, four were significantly enriched in healthy controls whereas other seven were significantly enriched in active phase of the disease. Several important pathways, such as ribosome biogenesis and Energy metabolism were depleted in the active phase. Our study has highlighted several taxa and functional categories that could be implicated with the onset of Crohn's disease and thus have the potential to serve as biomarkers of the active disease. However, these findings require further validation through functional studies in the future.

Infliximab for Crohn's Disease Patients with Perianal Fistulas: Better Image, Better Life.

BACKGROUND Patients with Crohn's disease (CD) experience physical impairments, poor quality of life and negative body image. These factors are exacerbated in CD patients with active perianal fistulas. MATERIAL AND METHODS Baseline characteristics were compared in retrospectively enrolled CD patients with and without active perianal fistulas. The relationships between improvements in perianal fistulas and quality of life, body image, and self-esteem were determined. The effects of infliximab treatment on improvement of psychological-social status were assessed in CD patients with active perianal fistulas. RESULTS Of the 301 CD patients included in our institution's database. 91 (30.2%) had active perianal fistulas. After adjustment by propensity score matching, CD patients with active perianal fistulas had lower self-esteem and more severe body image dissatisfaction than CD patients without active perianal fistulas (P<0.01 each). Perianal fistula response was closely associated with improvements in quality of life, body image dissatisfaction and self-esteem (P<0.01 each). Patients with perianal fistula treated with infliximab showed a response rate of 68.3%, significantly higher than the rate in patients with perianal fistula not treated with infliximab (P=0.005). Furthermore, improvements of life quality, body image and self-esteem were significantly greater in patients with perianal fistula who were than were not treated with infliximab (P<0.05 each). CONCLUSIONS CD patients with active perianal fistulas experience body image dissatisfaction, low self-esteem and poor quality of life. Treatment of these patients with infliximab could improve their body image, self-esteem and quality of life.

Applying Machine Learning Models to Predict Medication Nonadherence in Crohn's Disease Maintenance Therapy.

OBJECTIVE: Medication adherence is crucial in the management of Crohn's disease (CD), and yet the adherence remains low. This study aimed to develop machine learning models that can help predict CD patients of nonadherence to azathioprine (AZA), and thus assist caregivers to streamline the intervention process. METHODS: This single-centered, cross-sectional study recruited 446 CD patients who have been prescribed AZA between Sep 2005 and Sep 2018. Questionnaires of medication adherence, anxiety and depression, beliefs of medication necessity and concerns, and medication knowledge were provided to patients, while other data were extracted from the electronic medical records. Two machine learning models of back-propagation neural network (BPNN) and support vector machine (SVM) were developed and compared with logistic regression (LR), and assessed by accuracy, recall, precision, F1 score and the area under the receiver operating characteristic curve (AUC). RESULTS: The average classification accuracy and AUC of the three models were 81.6% and 0.896 for LR, 85.9% and 0.912 for BPNN, and 87.7% and 0.930 for SVM, respectively. Multivariate analysis identified four risk factors associated with AZA nonadherence: medication concern belief (OR=3.130, p<0.001), education (OR=2.199, p<0.001), anxiety (OR=1.549, p<0.001) and depression (OR=1.190, p<0.001), while medication necessity belief (OR=0.004, p<0.001) and medication knowledge (OR=0.805, p=0.013) were protective factors. CONCLUSION: We developed three machine learning models and proposed an SVM model with promising accuracy in the prediction of AZA nonadherence in Chinese CD patients. The study also reconfirmed that education, psychologic distress, and medication beliefs and knowledge are correlated to AZA nonadherence.

Patients' Educational Program Could Improve Azathioprine Adherence in Crohn's Disease Maintenance Therapy.

AIM: To determine the risk factors of nonadherence to azathioprine (AZA) maintenance therapy for Crohn's disease (CD) and to evaluate the influence of patients' educational program on adherence to AZA maintenance therapy. METHODS: Patients receiving AZA as maintenance therapy for CD were enrolled. Demographic data, clinical data, and usage information were collected. Univariate and multivariate analyses were performed to identify the risk factors of nonadherence. Then, patients' educational program was conducted. One year after the program, the improvements in adherence and relapse rates were compared between educational and noneducational groups. RESULTS: A total of 378 CD patients receiving AZA as maintenance therapy were enrolled from September 2008 to September 2018. Nonadherence occurred in 43.9% (166/378) of patients. Univariate analysis revealed that young age, education, alcoholism, anxiety, depression, concern belief, and lack of necessity belief and AZA knowledge were risk factors of nonadherence (P < 0.05). Multivariate logistic regression showed that anxiety (OR 6.244, 95% CI 2.563-15.213), depression (OR 3.801, 95% CI 1.281-11.278), and concern belief (OR 19.531, 95% CI 3.393-120.732) were independent risk factors of nonadherence. Necessity belief (OR 0.961, 95% CI 0.925-0.999) and AZA knowledge (OR 0.823, 95% CI 0.758-0.903) were protective factors of adherence. One year after the AZA educational program, the necessity belief, AZA knowledge, and adherence of the educational group significantly improved (P < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group (P < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, P = 0.035). CONCLUSIONS: Nonadherence occurred frequently in CD patients receiving AZA maintenance therapy. Educational programs could improve patients' adherence mainly by promoting their beliefs and knowledge of AZA and could reduce relapse rates during treatment.

The Diagnostic Yields and Safety of Double-Balloon Enteroscopy in Obscure Gastrointestinal Bleeding and Incomplete Small Bowel Obstruction: Comparison between the Adults and Elderly.

BACKGROUND: Double-balloon enteroscopy (DBE) is widely used worldwide. However, comparisons between the diagnostic yields in adults and the elderly remain scarce. AIM: The aim of this study is to compare the diagnostic yields and safety of DBE between adults and elderly with obscure gastrointestinal bleeding and incomplete small bowel obstruction. METHOD: We retrospectively reviewed patients who underwent DBE with indication of obscure gastrointestinal bleeding or incomplete small bowel obstruction in Ruijin Hospital and classified them into adults (18-64 years old) and elderly (≥65 years old). Clinical characteristics, diagnostic yields, and postoperative complications were collected and further analyzed. RESULTS: A total of 877 DBE procedures, 729 in adults and 148 in the elderly, were performed. In the patients with OGIB, the adults showed a higher frequency of Meckel's diverticulum compared with the elderly (4.6% vs. 0.9%, P = 0.032). Angioectasia was higher in frequency in the elderly than in the adults (25.9% vs. 17.9%, P = 0.048). In patients with incomplete small bowel obstruction, the elderly were more likely to have adenocarcinoma than the adults (19.4% vs. 7.1%, P = 0.038). The adults had higher tendency to have Crohn's disease than the elderly (23.4% vs. 8.3%, P = 0.045). Most of the postoperative complications were mild. The adults and elderly displayed comparable tolerance to DBE (P > 0.05). CONCLUSION: DBE has a high diagnostic yield in small bowel disorders, and a slight difference in disease spectrum was observed between the adults and elderly. DBE can be well-tolerated in the elderly.

Clinical characteristics of small bowel tumors diagnosed by double-balloon endoscopy: Experience from a Chinese tertiary hospital.

BACKGROUND/AIMS: To determine the characteristics of small bowel tumors (SBTs) in patients underwent double balloon endoscopy (DBE) and to compare the clinical value of DBE with other diagnostic tools. MATERIALS AND METHODS: A retrospective study was conducted in patients underwent DBE procedures from March 2008 to April 2017.The demographic, clinical and pathological characteristics of patients with SBTs were recorded, while the diagnosis of SBTs was achieved either by DBE biopsy or surgical specimens. RESULTS: One thousand one hundred and two patients (761 males, range 3-85 years) were enrolled in this study, with 1140 procedures completed in total. 99/1102 patients (9.0%) had SBTs, including benign polyps (20, 20.2%), gastrointestinal stromal tumors (GISTs) (24, 24.2%), lymphomas (13, 13.1%), adenocarcinoma (39, 39.4%), and neuroendocrine tumors (3, 3.0%). The most common clinical symptom for benign polyps was obscure gastrointestinal bleeding (OGIB) (75.0%). But among patients with malignant SBTs, the main indication for DBE was chronic abdominal pain (43.8%), followed by OGIB (36.3%), vomit (10.0%), abnormal images (6.3%) and diarrhea (3.8%) (P<0.001). Moreover, SBTs were primarily located in the jejunum alone (40/99, 40.4%). DBE had better sensitivity (89.2%), specificity (95.2%), positive predictive value (PPV) (90.0%), and negative predictive value (NPV) (94.8%) than other tools for suspected SBTs. CONCLUSION: Small bowel tumor is mainly located in jejunum and with OGIB and abdominal pain as major complaints. DBE is a reliable method for the diagnosis of SBTs compared with other diagnostic tools.

TRIM29 facilitates the epithelial-to-mesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Tripartite Motif 29 (TRIM29) has been newly identified as being implicated in cancer progression. However, the biological role and molecular mechanism of TRIM29 in the invasion and metastasis of colorectal cancer (CRC) remain to be determined. METHODS: The expression levels of TRIM29 and ß-catenin in CRC patient specimens were detected by immunohistochemistry. Recombinant lentivirus vectors containing the TRIM29 gene and its small hairpin interfering RNAs were constructed and transduced into CRC cells. Wound-healing and Transwell assays were performed to evaluate the migration and invasion abilities of CRC cells in vitro. Hepatic metastasis models in nude mice were established to validate the function of TRIM29 in vivo. Moreover, the expressions of epithelial-to-mesenchymal transition (EMT)-associated proteins were detected by qRT-PCR and Western blotting in CRC cells. Finally, Western blotting, qRT-PCR, luciferase reporter assays, and immunofluorescence assays were used to explore the molecular mechanisms of TRIM29 in CRC progression. RESULTS: Increased TRIM29 expression positively correlated with lymph node metastasis and ß-catenin expression in patient CRC tissues. Overexpression of TRIM29 promoted invasion and metastasis of CRC cells in vitro and in vivo by regulating EMT, whereas the knockdown of TRIM29 had the opposite effect. Further mechanistic studies suggest that TRIM29 can activate the Wnt/ß-catenin signaling pathway via up-regulating CD44 expression in colorectal cancer. CONCLUSIONS: TRIM29 induces EMT through activating the Wnt/ß-catenin signaling pathway via up-regulating CD44 expression, thus promoting invasion and metastasis of CRC.

Improvement of psychological status after infliximab treatment in patients with newly diagnosed Crohn's disease.

BACKGROUND: Patients with newly diagnosed Crohn's disease (CD) are associated with impaired physical and psychological well-being. These psychological characteristics are dynamic with the course of disease and could be influenced by medical treatment. Infliximab is effective and widely used in moderate-to-severe CD patients. The aim of this study was to evaluate the improvement of psychological status after infliximab treatment in patients with newly diagnosed CD. METHODS: Newly diagnosed moderate-to-severe CD patients were prospectively enrolled in our study. Infliximab 5 mg/kg was administered at weeks 0, 2, 6, 14, 22, and 30. Outcomes including disease severity, illness perceptions, coping strategies, anxiety, depression, and quality of life (QoL) were measured at baseline, week 14, and week 30. RESULTS: Eighty-two patients completed our study. The rates of clinical remission at weeks 14 and 30 were 59/82 (72.0%) and 58/82 (70.7%), respectively. Patients who achieved clinical remission at weeks 14 and 30 significantly improved in illness perceptions (P<0.001 and <0.001), maladaptive coping (P=0.005 and 0.004), anxiety (P<0.001 and <0.001), depression (P=0.004 and 0.004), and QoL (P<0.001 and <0.001). However, emotion-focused coping and problem-focused coping remained unchanged. For infliximab nonresponders, no significant changes were seen in illness perceptions, coping strategies, anxiety, depression, or QoL at week 14 or 30. CONCLUSION: Effective infliximab treatment not only led to clinical remission in patients with newly diagnosed moderate-to-severe CD but also improved their psychological status including illness perceptions, maladaptive coping, anxiety, depression, and QoL.