Publications by authors named "Zhengting Wang"

62 Publications

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

Cell Rep Med 2021 Aug 27;2(8):100353. Epub 2021 Jul 27.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, and the Ministry of Education Key Laboratory of Cell Death and Differentiation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xcrm.2021.100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385246PMC
August 2021

ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells.

J Clin Invest 2021 Aug 17. Epub 2021 Aug 17.

Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic programme and function in the tumor microenvironment (TME) remain elusive. Here, we show a Zinc finger protein 91 (ZFP91)-governed mechanism disrupting the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA sequencing revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from colorectal cancer patients. T cell-specific deletion of Zfp91 led to enhanced T cell proliferation and potentiated T cell antitumor function. Loss of ZFP91 increased mammalian target of rapamycin complex 1 (mTORC1) activity to drive T cell glycolysis. Mechanistically, T cell antigen receptor (TCR)-dependent ZFP91 cytosolic translocation promoted protein phosphatase 2A (PP2A) complex assembly, thereby restricting mTORC1-mediated metabolic reprogramming. Our results demonstrate that ZFP91 perturbs T cell metabolic and functional states in the TME and suggest that targeting ZFP91 may improve the efficacy of cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI144318DOI Listing
August 2021

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

Acta Biochim Biophys Sin (Shanghai) 2021 Aug 6. Epub 2021 Aug 6.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/abbs/gmab106DOI Listing
August 2021

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

Adv Sci (Weinh) 2021 Sep 22;8(18):e2101619. Epub 2021 Jul 22.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202101619DOI Listing
September 2021

A resident stromal cell population actively restrains innate immune response in the propagation phase of colitis pathogenesis in mice.

Sci Transl Med 2021 07;13(603)

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China.

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E (PGE). PGE induction requires a nuclear factor κB-independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not or , in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (T1)/T17 infiltration and aggravated colitis development. PGE administration ameliorated colitis in mouse models with defective PGE production but not in animals with normal PGE induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE biosynthesis, in inflamed tissues, and especially in colon VimentinTwist2 stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abb5071DOI Listing
July 2021

mA demethylase ALKBH5 controls CD4 T cell pathogenicity and promotes autoimmunity.

Sci Adv 2021 Jun 16;7(25). Epub 2021 Jun 16.

Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

N-methyladenosine (mA) modification is dynamically regulated by "writer" and "eraser" enzymes. mA "writers" have been shown to ensure the homeostasis of CD4 T cells, but the "erasers" functioning in T cells is poorly understood. Here, we reported that mA eraser AlkB homolog 5 (ALKBH5), but not FTO, maintains the ability of naïve CD4 T cells to induce adoptive transfer colitis. In addition, T cell-specific ablation of ALKBH5 confers protection against experimental autoimmune encephalomyelitis. During the induced neuroinflammation, ALKBH5 deficiency increased mA modification on interferon-γ and C-X-C motif chemokine ligand 2 messenger RNA (mRNA), thus decreasing their mRNA stability and protein expression in CD4 T cells. These modifications resulted in attenuated CD4 T cell responses and diminished recruitment of neutrophils into the central nervous system. Our findings reveal an unexpected specific role of ALKBH5 as an mA eraser in controlling the pathogenicity of CD4 T cells during autoimmunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abg0470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208713PMC
June 2021

Ubc13 Promotes K63-Linked Polyubiquitination of NLRP3 to Activate Inflammasome.

J Immunol 2021 05 23;206(10):2376-2385. Epub 2021 Apr 23.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of NLRP3 has been shown to be essential for its activation, yet the functions of Ubc13, the K63-linked specific ubiquitin-conjugating enzyme E2, in NLRP3 inflammasome activation are not known. In this study, we found that in mouse macrophages, Ubc13 knockdown or knockout dramatically impaired NLRP3 inflammasome activation. Catalytic activity is required for Ubc13 to control NLRP3 activation, and Ubc13 pharmacological inhibitor significantly attenuates NLRP3 inflammasome activation. Mechanistically, Ubc13 associates with NLRP3 and promotes its K63-linked polyubiquitination. Through mass spectrum and biochemical analysis, we identified lysine 565 and lysine 687 as theK63-linked polyubiquitination sites of NLRP3. Collectively, our data suggest that Ubc13 potentiates NLRP3 inflammasome activation via promoting site-specific K63-linked ubiquitination of NLRP3. Our study sheds light on mechanisms of NLRP3 inflammasome activation and identifies that targeting Ubc13 could be an effective therapeutic strategy for treating aberrant NLRP3 inflammasome activation-induced pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2001178DOI Listing
May 2021

The effects and mechanism of Kangfuxin on improving healing quality and preventing recurrence of gastric ulcer.

Biomed Pharmacother 2021 Jun 23;138:111513. Epub 2021 Mar 23.

Sichuan Key Laboratory of Medical American Cockroach, Chengdu, Sichuan 610000, China. Electronic address:

This study investigated the gastroprotective effects and possible mechanism of Kangfuxin (KFX), an ethanol extract of Periplaneta americana L. (Dictyoptera; Blattidae), on improving healing quality and preventing recurrence of gastric ulcer. The effects of KFX were investigated in patients treated with endoscopic submucosal dissection (ESD), gastric ulcer animal model, and rat gastric mucosal cells and fibroblasts. Moreover, the relationship between KFX and p38/NF-κB pathway were explored both in vivo and in vitro. In patients, KFX exhibited protective effects against gastric ulcers and resulted in a decrease in the CD3 expression. In vivo animal experiments confirmed that KFX accelerated ulcer healing by promoting neovascularization (increased CD34 expression), suppressing inflammation (decreased interleukin-1β (IL-1β), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and IL-8 expression), and enhancing growth factor expression, including the epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF). In vitro experiments demonstrated that treatment with 10% KFX rat serum decreased IL-1β, IL-1Ra, SIL-1RAP, TNF-α, and ICAM-1 expression in rat gastric mucosal cells or fibroblasts and increased IL-1R expression compared to that in the group treatment with 10% normal rat serum. Furthermore, KFX inhibited the activation of p38/NF-κB pathway both in vivo and in vitro. In conclusion, KFX treatment could effectively improve healing quality and prevent gastric ulcer recurrence, which might be attributed to neovascularization, suppressed inflammation, and enhanced growth factor expression. The p38/NF-κB pathway may be one of important mechanism to mediate the effects of KFX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111513DOI Listing
June 2021

SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function.

Mol Cell 2021 03;81(5):940-952.e5

Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China. Electronic address:

STING-dependent cytosolic DNA sensing in dendritic cells (DCs) initiates antitumor immune responses, but how STING signaling is metabolically regulated in the tumor microenvironment remains unknown. Here, we show that oxidative stress is required for STING-induced DC antitumor function through a process that directs SUMO-specific protease 3 (SENP3) activity. DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon (IFN) signaling in DCs and dampening antitumor immune responses. DC-derived reactive oxygen species (ROS) trigger SENP3 accumulation and the SENP3-IFI204 interaction, thereby catalyzing IFI204 deSUMOylation and boosting STING signaling activation in mice. Consistently, SENP3 senses ROS to facilitate STING-dependent DC activity in tissue samples from colorectal cancer patients. Our results reveal that oxidative stress as a metabolic regulator promotes STING-mediated DC antitumor immune responses and highlights SENP3 as an overflow valve for STING signaling induction in the metabolically abnormal tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molcel.2020.12.024DOI Listing
March 2021

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

Med Sci Monit 2020 Nov 3;26:e926635. Epub 2020 Nov 3.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.926635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648406PMC
November 2020

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

Front Cell Infect Microbiol 2020 6;10:544704. Epub 2020 Oct 6.

Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Institute of Immunology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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 β diversities were significantly lower during the active phase in contrast with remission phase and healthy samples. In general, were most abundant among the three sample groups, followed by and . Genus level distribution highlighted , and 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_, f_, and p_. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2020.544704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574453PMC
June 2021

Cutting Edge: Inhibition of Glycogen Synthase Kinase 3 Activity Induces the Generation and Enhanced Suppressive Function of Human IL-10 FOXP3-Induced Regulatory T Cells.

J Immunol 2020 09 19;205(6):1497-1502. Epub 2020 Aug 19.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

IL-10 is critical for Foxp3 regulatory T cell (Tregs)-mediated immune suppression, but how to efficiently upregulate IL-10 production in Tregs remains unclear. In this article, we show that human IL-10 FOXP3-induced regulatory T cell (iTreg) generation can be dramatically promoted by inhibiting GSK3 activity. IL-10 FOXP3 iTregs induced by GSK3 inhibition exhibit classical features of immune-suppressive T cells. We further demonstrate that IL-10 iTregs exhibit enhanced suppressive function in both IL-10-dependent and -independent manners. The enhanced suppressive function of IL-10 Tregs is not due to a single factor such as IL-10, although IL-10 may mediate this enhanced suppressive function to some extent. Mechanistically, the increased transcriptional activity of IL-10 promoter and the enhanced expression of C-Maf and BLIMP1 coordinately facilitate IL-10 expression in human iTregs under GSK3 inhibition. Our study provides a new strategy to generate human immune-suppressive IL-10 FOXP3 Tregs for immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477744PMC
September 2020

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

Med Sci Monit 2020 Aug 12;26:e925018. Epub 2020 Aug 12.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.925018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444618PMC
August 2020

MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis.

Sci China Life Sci 2021 Mar 28;64(3):389-403. Epub 2020 Jul 28.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, and Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.

T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity, a known cause of inflammatory bowel disease. However, precisely how T cells regulate intestine immunity remains to be fully understood. In this study, we found that mitogen-activated protein kinase kinase kinase 2 (MAP3K2) is required for the CD4 T cell-mediated inflammation in the intestine. Using a T cell transfer colitis model, we found that MAP3K2-deficient naïve CD4 T cells had a dramatically reduced ability to induce colitis compared to wild type T cells. In addition, significantly fewer IFN-γ- but more IL-17A-producing CD4 T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed. Interestingly, under well-defined in vitro differentiation conditions, MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1, Th17 and Treg. Furthermore, the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine. At the molecular level, we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation. Together, our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1720-9DOI Listing
March 2021

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

Patient Prefer Adherence 2020 3;14:917-926. Epub 2020 Jun 3.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/PPA.S253732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280067PMC
June 2020

DKK2 blockage-mediated immunotherapy enhances anti-angiogenic therapy of Kras mutated colorectal cancer.

Biomed Pharmacother 2020 Jul 20;127:110229. Epub 2020 May 20.

Department of Pharmacology and Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT, United States. Electronic address:

There are limited options for targeted therapies for colorectal cancer (CRC). Anti-EGFR therapy is limited to CRC without KRAS mutations. Even worse, most of CRC are refractory to currently immune checkpoint blockade. DKK2, which is upregulated in CRC, was recently found to suppress host immune responses, and its blockage effectively impeded tumor progression in benign genetic CRC models in our previous study. Here, our recent study demonstrated that in human CRC tumor samples expressing high levels of DKK2, DKK2 blockade caused stronger activation of tumor infiltrating CD8 T cells in ex vivo culture. Intriguingly, we observed a correlation of high DKK2 expression with increased lymph node metastasis prevalence in these CRC patients as well. Furthermore, in a mouse genetic CRC model with mutations in APC and KRAS, which more closely mimics advanced human CRC, we confirmed the tumor inhibitory effect of DKK2 blockade, which significantly retarded tumor progression and extended survival, with increased immune effector cell activation and reduced angiogenesis. Based on this, we performed a combined administration of DKK2 blockade with sub-optimal anti-VEGFR treatment and observed a synergetic effect on suppressing tumor angiogenesis and progression, as well as extending survival, better than those of every single therapy. Thus, this study provides further evidence for the potential therapeutic application of DKK2 blockade in the clinical treatment of human CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2020.110229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523634PMC
July 2020

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

Gastroenterol Res Pract 2020 27;2020:8121625. Epub 2020 Apr 27.

Department of Gastroenterology, Ruijin Hospital, Shanghai, Jiaotong University School of Medicine, Shanghai, China.

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%, = 0.032). Angioectasia was higher in frequency in the elderly than in the adults (25.9% vs. 17.9%, = 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%, = 0.038). The adults had higher tendency to have Crohn's disease than the elderly (23.4% vs. 8.3%, = 0.045). Most of the postoperative complications were mild. The adults and elderly displayed comparable tolerance to DBE ( > 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8121625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201743PMC
April 2020

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

Gastroenterol Res Pract 2020 20;2020:6848293. Epub 2020 Apr 20.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

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 ( < 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 ( < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group ( < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/6848293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189306PMC
April 2020

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

Turk J Gastroenterol 2020 01;31(1):30-35

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5152/tjg.2020.19115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075680PMC
January 2020

Re-emergence of scrub typhus in Zhejiang Province, southern China: A 45-year population-based surveillance study.

Travel Med Infect Dis 2019 May 21. Epub 2019 May 21.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China; Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China. Electronic address:

Background: Scrub typhus is the leading cause of treatable unidentified febrile illnesses in Southeast Asia. This study was conducted to document the epidemiological characteristics of scrub typhus and its change in Zhejiang, one of traditional epidemic provinces in China.

Methods: Scrub typhus surveillance data in Zhejiang province during 1957-1989 and 2006-2012 were obtained. Descriptive analysis was conducted to characterize the epidemiology of scrub typhus. The spatial distributions over the periods were explored using spatial autocorrelation analysis and spatiotemporal cluster analysis.

Results: A total of 4104 cases and 7 deaths were reported from 1957 to 1989 and 2006 to 2017. The incidence declined since 1959, remained low from 1967 to 1989, and then exponentially increased after 2006. The seasonality changed from a summer pattern between 1957 and 1989 to a bimodal peak pattern in July to August and October to November from 2006 to 2017. One primary and three secondary high-risk clusters were affirmed in both periods from 1980 to 1989 and 2006 to 2017. The primary cluster expanded southwestward and the time span of the secondary clusters extended in the later period compared to the clusters in the previous time frame.

Conclusion: Zhejiang recently underwent a seasonality change, geographic extension, and incidence increase in scrub typhus. More attention should be paid to controlling scrub typhus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tmaid.2019.05.013DOI Listing
May 2019

Different Associations between Promoter-336G/A () Polymorphism with Severe Dengue in Asians and South-Central Americans: a Meta-Analysis.

Int J Environ Res Public Health 2019 04 25;16(8). Epub 2019 Apr 25.

Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou 310051, China.

: This study was conducted to identify the association between polymorphism in with the susceptibility of severe dengue. : A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). : A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession ( versus : OR = 0.44, 95%CI, 0.23-0.82) and a codominant model ( versus : OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in was a risk factor for severe dengue under dominant ( versus : OR = 1.86,95%CI, 1.01-3.45), superdominant ( versus : OR = 1.81,95%CI, 1.02-3.21) and a codominant ( versus : OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive ( versus : OR = 0.27,95%CI, 0.10-0.70) and codominant ( versus : OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. : Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin () promoter-336G/A () polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph16081475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518176PMC
April 2019

Factors Correlating to the Development of Hepatitis C Virus Infection in Hemodialysis Patients-Findings Mainly from Asiatic Populations: A Systematic Review and Meta-Analysis.

Int J Environ Res Public Health 2019 04 24;16(8). Epub 2019 Apr 24.

Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China.

Hemodialysis is an effective replacement therapy for chronic renal failure patients. In recent decades, the number of hemodialysis patients has grown rapidly and some measures for preventing blood-borne diseases have been implemented, but hepatitis C virus (HCV) infection remains a significant problem. The meta-analysis published in 2009 on HCV infection-related factors was based on localized study objects, and some additional studies have been published since 2009; however, the contribution of these factors remains under dispute. Our study pooled the odds ratios (ORs) or mean standard deviations (MDs) with 95% confidence intervals (CIs) and analyzed sensitivity using Review Manager 5.1 software (5.1 version Copenhagen: The Nordic Cochrane Centre; 2011) by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Spearman correlation analysis was performed using the SPSS package. In our meta-analysis, 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients from 44 studies were analyzed. The pooled ORs with 95% CIs were: histories of blood transfusion, 4.30 (3.11, 5.96); weekly hemodialysis times > 2, 6.00 (3.25, 11.06); kidney transplantation, 5.80 (3.95, 8.52); hemodialysis units > 2, 6.90 (2.42, 19.68); shared hemodialysis devices, 5.00 (2.35, 10.65); and drug addiction, 4.73 (1.54, 14.47). The pooled MDs with 95% CIs were duration of hemodialysis (months) 27.48 (21.67, 33.30). There was a positive correlation between duration of hemodialysis and the HCV infection rate ( < 0.01). Hemodialysis patients, especially from Asia, with shared hemodialysis devices, hemodialysis units > 2, blood transfusion, kidney transplantation, and drug addiction were at increased risk of HCV infection. The HCV infection rate increased with the duration of hemodialysis. High-risk hemodialysis patients should be monitored and receive timely screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph16081453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518179PMC
April 2019

Antibiotics exacerbated colitis by affecting the microbiota, Treg cells and SCFAs in IL10-deficient mice.

Biomed Pharmacother 2019 Jun 8;114:108849. Epub 2019 Apr 8.

Department of Gastroenterology of Ruijin Hospital, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Pharmacology, Yale University School of Medicine, CT, 06511, USA. Electronic address:

Many studies have shown that antibiotic therapy can attenuate colitis in IL10-deficient (IL10) mice. However, these results have indicated that antibiotics were more successful in preventing, rather than treating established colitis. Those antibiotic treatments attempted to only partially alter the intestinal microbiota and to not eliminate it completely. Therefore, we treated IL10 mice with the multiantibiotic regimen that was used to develop a pseudo-germ-free mouse model to determine whether multi-antibiotics attenuated or exacerbated colitis. We evaluated the colitis in IL10 mice receiving the antibiotic treatment versus those receiving the water control; furthermore, we investigated the gut microbiota, the intestinal immune cell proportions and the cytokine secretion. Surprisingly, the IL10 mice receiving the antibiotic treatment had more severe intestinal colitis and a swollen cecum than those receiving the water control. Moreover, the abundance of microbiota and content of short-chain fatty acids (SCFAs) in the colon were dramatically decreased. Additionally, the proportions of Treg cells and Th1 cells in the colons of IL10 mice were also decreased. The mechanism may be that the decrease in the microbiota leads to a decrease in the proportions of Treg cells and SCFAs, which are necessary to maintain intestinal homeostasis. All changes lead to further exacerbated colitis in IL10 mice with antibiotic treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2019.108849DOI Listing
June 2019

Surgical Compliance and Outcomes in Gastric Cancer: a population-based cohort study.

J Cancer 2019 2;10(4):779-788. Epub 2019 Feb 2.

Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.

Surgical resection is one of curative treatment for gastric cancer (GC), however, a set of patients show poor surgical compliance in the USA. We aimed to identify the risk factors associated with surgical compliance and investigate the difference in survival. GC patients diagnosed between 1973 and 2014 were identified from the Surveillance Epidemiology and End Results (SEER) databases. Based on different surgical compliance and treatment regimen, patients were classified into three subgroups: surgical compliance group, surgical noncompliance group, and non-surgical group. Multivariable Logistic regression analysis was adopted to identify the factors related to surgical compliance; Multivariable Cox regression was used to investigate the prognostic factors. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier estimator method. Of 79374 GC patients who were recommended for surgical therapy, 15201(19.2%) cases did not perform surgery. Poor compliance of surgery was related to old age, American Indian/Alaska Native race, poor grading/late staging, single/widowed status, lower socioeconomic status and earlier time of diagnosis. As expected, GC patients of surgical compliance group showed significantly more favorable survival than the other two groups (P<0.0001); notably, the outcome of surgical noncompliance group came close to that of non-surgical group. GC patients of poor surgical compliance demonstrated adverse survival, which was comparable to that of non-surgical patients. The poor surgical compliance was associated with older age, American Indian/Alaska Native race, poor tissue differentiation/advanced stage of tumor, single/widowed status, lower socioeconomic status and earlier time of diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.29073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400806PMC
February 2019

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

J Exp Clin Cancer Res 2019 Feb 27;38(1):104. Epub 2019 Feb 27.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

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 β-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 β-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/β-catenin signaling pathway via up-regulating CD44 expression in colorectal cancer.

Conclusions: TRIM29 induces EMT through activating the Wnt/β-catenin signaling pathway via up-regulating CD44 expression, thus promoting invasion and metastasis of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-019-1098-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391790PMC
February 2019

Beneficial effects of dual TORC1/2 inhibition on chronic experimental colitis.

Int Immunopharmacol 2019 May 20;70:88-100. Epub 2019 Feb 20.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 200025 Shanghai, PR China. Electronic address:

Background And Aim: AZD8055, a new immunosuppressive reagent, a dual TORC1/2 inhibitor, had been used successfully in animal models for heart transplantation. The aim of this study was to evaluate the effects and mechanisms of AZD8055 on chronic intestinal inflammation.

Methods: Dextran sulfate sodium (DSS) - induced chronic colitis was used to investigate the effects of AZD8055 on the development of colitis. Colitis activity was monitored by body weight assessment, colon length, histology and cytokine profile analysis.

Results: AZD8055 treatment significantly alleviated the severity of colitis, as assessed by colonic length and colonic damage. In addition, AZD8055 treatment decreased the colonic CD4+ T cell numbers and reduced both Th1 and Th17 cell activation and cytokine production. The percentages of Treg cells in the colon were also expanded by AZD8055 treatment. Furthermore, AZD8055 effectively inhibited mTOR downstream proteins and signal transducer and activator of transcription related proteins in CD4+ T cells of intestinal lamina propria.

Conclusions: These findings increased our understanding of DSS-induced colitis and shed new lights on mechanisms of digestive tract chronic inflammation. Dual TORC1/2 inhibition showed potent anti-inflammatory and immune regulation effects by targeting critical signaling pathways. The results supported the strategy of using dual mTOR inhibitor to treat inflammatory bowel disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2019.02.022DOI Listing
May 2019

Correction: Inhibition of neddylation regulates dendritic cell functions Deptor accumulation driven mTOR inactivation.

Oncotarget 2018 12 18;9(99):37343. Epub 2018 Dec 18.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

[This corrects the article DOI: 10.18632/oncotarget.9543.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.26504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324676PMC
December 2018

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

Patient Prefer Adherence 2018 21;12:879-885. Epub 2018 May 21.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

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 (<0.001 and <0.001), maladaptive coping (=0.005 and 0.004), anxiety (<0.001 and <0.001), depression (=0.004 and 0.004), and QoL (<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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/PPA.S156883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973631PMC
May 2018

Prognostic Analysis of Duodenal Gastrointestinal Stromal Tumors.

Gastroenterol Res Pract 2018 20;2018:4812703. Epub 2018 Feb 20.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Aim: This study aims to analyze factors possibly related to the prognosis of duodenal gastrointestinal stromal tumors (DGISTs).

Methods: We collected and retrospectively analyzed clinical and pathological data of 62 patients with primary DGISTs. All the patients were hospitalized and received complete surgical resection at Shanghai Ruijin Hospital from September 2003 to April 2015. We followed up the patients to determine survival outcomes. We also analyzed the effect of clinical and pathological factors on disease-free survival (DFS) and overall survival (OS) of the patients.

Results: Kaplan-Meier univariate survival analysis demonstrated that tumor size, mitotic index, Ki-67 index, and pathological risk were correlated with the DFS and OS of the patients (DFS = 0.039, 0.001, <0.001, and 0.005, resp.; OS = 0.027, 0.007, <0.001, and 0.012, resp.). Cox multivariate regression analysis revealed that Ki-67 index was an independent prognostic factor affecting DFS and OS ( = 0.007 and 0.028, resp.). Moreover, Kaplan-Meier survival analysis showed that imatinib treatment for patients with recurrence was correlated with prolonged OS ( = 0.002).

Conclusion: Prognosis for DGIST treated by R0 resection is favorable. High level of Ki-67 can be an independent risk factor of DGIST prognosis. Adjuvant imatinib therapy for patients with tumor recurrence could probably lead to prolonged survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/4812703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838428PMC
February 2018
-->