An education-based telehealth group improves the management and clinical outcomes of patients with inflammatory bowel disease in China (THEIM study).

BACKGROUND: Although poor medication adherence has a negative impact on disease prognosis in patients with inflammatory bowel disease (IBD), finding proven solutions remains a challenge. In this study, we developed a telehealth management model based on education and patient-centered medical care (PCEB) using the social media platform WeChat. OBJECTIVE: To investigate the effect of PCEB on adherence and clinical outcomes. METHODS: In this retrospective cohort, 543 IBD patients (274 in the PCEB group and 269 in the routine group) at the IBD center of Renmin Hospital (Wuhan University, Wuhan, China) were enrolled between January 2020 and September 2022. The routine group received routine follow-up and management, while for PCEB patients, a comprehensive IBD education program and PCEB were conducted. Medication adherence and clinical outcomes were also evaluated. RESULTS: There were no differences between the PCEB and routine groups in terms of patient demographics and clinical characteristics, including disease classification, duration, biological treatment, and educational background at baseline. Compared with routine treatment, PCEB greatly improved patient medication adherence, as assessed by compliance with oral medication, enteral nutrition, biological infusion, and scheduled endoscopic assessment. Clinical and endoscopic remission in patients with PCEB increased during short-term (month 4) and long-term (month 12) follow-ups, along with a decrease in relapse rates for CD (13.3% vs. 31.8%) and UC (19.8% vs. 37.2%). CONCLUSION: The telehealth model applied to the PCEB group improved medication adherence and clinical outcomes in patients with IBD. This is a new and powerful solution for the long-term management of this chronic and progressive disease.

CaMKII Mediates TGFß1-Induced Fibroblasts Activation and Its Cross Talk with Colon Cancer Cells.

INTRODUCTION: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. TGFß1 has been the mostly accepted factor to fuel normal fibroblasts transformation into CAFs. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is thought to play an important role in fibroblasts activation induced by TGFß1. The aim of this study is to investigate the potential role of CaMKII in TGFß1-induced fibroblasts activation and CAF-like differentiation. Cross talk between CaMKII-dependent fibroblasts and colon cancer in colon cancer progression also was addressed RESULTS: Immunostaining demonstrated that in colon cancer stroma, CaMKII overexpressed in stromal CAFs. In vitro, TGFß1 increased CAF markers expression in human colon fibroblasts CCD-18Co, but not in CaMKII depletion fibroblasts. CaMKII knockdown by CaMKII shRNA significantly inhibited TGFß1-induced fibroblasts activation and CAF-like differentiation. Smad3, AKT, and MAPK were targeted in TGFß1-CaMKII-mediated pathway. Human colon cancer cell line HCT-116 activated fibroblasts directly, whereas CaMKII depletion dragged CCD-18Co fibroblasts undergoing CAF-associated trans-differentiation. Furthermore, increased proliferation, migration, and invasion of colon cancer cells were stimulated when co-cultured with normal fibroblasts, but not with CaMKII depletion fibroblasts. CONCLUSIONS: These findings provide evidence that CaMKII is a critical mediator in TGFß1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.

Host-Induced Gene Silencing of a Multifunction Gene Sscnd1 Enhances Plant Resistance Against Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a devastating necrotrophic fungal pathogen and has a substantial economic impact on crop production worldwide. Magnaporthe appressoria-specific (MAS) proteins have been suggested to be involved in the appressorium formation in Magnaporthe oryzae. Sscnd1, an MAS homolog gene, is highly induced at the early infection stage of S. sclerotiorum. Knock-down the expression of Sscnd1 gene severely reduced the virulence of S. sclerotiorum on intact rapeseed leaves, and their virulence was partially restored on wounded leaves. The Sscnd1 gene-silenced strains exhibited a defect in compound appressorium formation and cell integrity. The instantaneous silencing of Sscnd1 by tobacco rattle virus (TRV)-mediated host-induced gene silencing (HIGS) resulted in a significant reduction in disease development in tobacco. Three transgenic HIGS Arabidopsis lines displayed high levels of resistance to S. sclerotiorum and decreased Sscnd1 expression. Production of specific Sscnd1 siRNA in transgenic HIGS Arabidopsis lines was confirmed by stem-loop qRT-PCR. This study revealed that the compound appressorium-related gene Sscnd1 is required for cell integrity and full virulence in S. sclerotiorum and that Sclerotinia stem rot can be controlled by expressing the silencing constructs of Sscnd1 in host plants.

Sclerotinia sclerotiorum Thioredoxin1 (SsTrx1) is required for pathogenicity and oxidative stress tolerance.

Sclerotinia sclerotiorum infects host plant tissues by inducing necrosis to source nutrients needed for its establishment. Tissue necrosis results from an enhanced generation of reactive oxygen species (ROS) at the site of infection and apoptosis. Pathogens have evolved ROS scavenging mechanisms to withstand host-induced oxidative damage. However, the genes associated with ROS scavenging pathways are yet to be fully investigated in S. sclerotiorum. We selected the S. sclerotiorum Thioredoxin1 gene (SsTrx1) for our investigations as its expression is significantly induced during S. sclerotiorum infection. RNA interference-induced silencing of SsTrx1 in S. sclerotiorum affected the hyphal growth rate, mycelial morphology, and sclerotial development under in vitro conditions. These outcomes confirmed the involvement of SsTrx1 in promoting pathogenicity and oxidative stress tolerance of S. sclerotiorum. We next constructed an SsTrx1-based host-induced gene silencing (HIGS) vector and mobilized it into Arabidopsis thaliana (HIGS-A) and Nicotiana benthamiana (HIGS-N). The disease resistance analysis revealed significantly reduced pathogenicity and disease progression in the transformed genotypes as compared to the nontransformed and empty vector controls. The relative gene expression of SsTrx1 increased under oxidative stress. Taken together, our results show that normal expression of SsTrx1 is crucial for pathogenicity and oxidative stress tolerance of S. sclerotiorum.

Diagnosis and therapy using double-balloon endoscopy for small bowel disease: experience from a Chinese tertiary hospital.

OBJECTIVE: To evaluate the clinical efficacy of double-balloon endoscopy (DBE) for small bowel disease (SBD). METHODS: The clinical and endoscopic data of patients who underwent DBE in a Chinese tertiary hospital from January 2006 to December 2019 were retrospectively reviewed. The patients were divided into three groups by age: the young group (<45 years), middle-aged group (45-65 years), and older group (>65 years). RESULTS: In total, 1177 patients who underwent 2134 DBE procedures were included. The anterograde and retrograde route was used in 1111 and 1023 procedures, respectively. The most common reason for performing DBE was suspected small bowel bleeding (SSBB) (53.1%), and the most common SBD was Crohn's disease (CD) (18.1%). Hemostasis was the predominant endoscopic therapy (54.3%). The total complication rate was 0.8%. The incidence of CD was highest in the young group, and the incidence of tumors was highest in the older group; these findings were consistent both among the overall patient population and among patients with SSBB. CONCLUSIONS: DBE is effective and safe for the diagnosis and treatment of SBD and is considered to have great potential as a first-line method for diagnosing SBD.

Glandular orientation and shape determined by computational pathology could identify aggressive tumor for early colon carcinoma: a triple-center study.

BACKGROUND: Identifying the early-stage colon adenocarcinoma (ECA) patients who have lower risk cancer vs. the higher risk cancer could improve disease prognosis. Our study aimed to explore whether the glandular morphological features determined by computational pathology could identify high risk cancer in ECA via H&E images digitally. METHODS: 532 ECA patients retrospectively from 2 independent data centers, as well as 113 from The Cancer Genome Atlas (TCGA), were enrolled in this study. Four tissue microarrays (TMAs) were constructed across ECA hematoxylin and eosin (H&E) stained slides. 797 quantitative glandular morphometric features were extracted and 5 most prognostic features were identified using minimum redundancy maximum relevance to construct an image classifier. The image classifier was evaluated on D2/D3 = 223, D4 = 46, D5 = 113. The expression of Ki67 and serum CEA levels were scored on D3, aiming to explore the correlations between image classifier and immunohistochemistry data and serum CEA levels. The roles of clinicopathological data and ECAHBC were evaluated by univariate and multivariate analyses for prognostic value. RESULTS: The image classifier could predict ECA recurrence (accuracy of 88.1%). ECA histomorphometric-based image classifier (ECAHBC) was an independent prognostic factor for poorer disease-specific survival [DSS, (HR = 9.65, 95% CI 2.15-43.12, P = 0.003)]. Significant correlations were observed between ECAHBC-positive patients and positivity of Ki67 labeling index (Ki67Li) and serum CEA. CONCLUSION: Glandular orientation and shape could predict the high risk cancer in ECA and contribute to precision oncology. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.

Emergent Double Balloon Enteroscopy in Overt Suspected Small Bowel Bleeding: Diagnosis and Therapy.

BACKGROUND Double balloon enteroscopy (DBE) is a diagnosis and therapy method for suspected small bowel bleeding (SSBB). The data for emergent DBE is limited in overt SSBB cases. The aim of this study was to investigate the role of diagnosis and therapy of emergent DBE in patients with overt SSBB. MATERIAL AND METHODS The clinical and endoscopic data for patients with overt SSBB undergoing DBE in a single center from January 2010 to December 2017 were collected and analyzed. Emergent DBE was defined as DBE performed less than 3 days of last bleeding onset. RESULTS A total of 265 DBEs in 265 patients with overt SSBB were enrolled (mean age, 44.7±17.3 years; 66.8% males). The patients were divided into 3 groups according to the timing of DBE: less than 3 days (n=32), more than 3 days and less than 7 days (n=146), and more than 7 days (n=87) (first group was the emergent group, the latter 2 groups were the non-emergent groups). The diagnosis yield for the emergent group was significantly higher than the non-emergent groups (84.4% versus 65.1% or 59.8%, respectively, P<0.05), but was not different between the 2 non-emergent groups (P>0.05). The top 3 diagnoses were angioectasias (19.6%), diverticulum (16.2%), and tumor (12.1%). For therapy yield, there was a remarkable reducing trend in the emergent group (<3 days), and the 2 non-emergent groups (3 to 7 days group and >7 days group: 78.1%, 58.2% and 39.1%, respectively, P<0.05. The top 3 endoscopic treatments were hemostatic clips (21.9%), argon plasma coagulation (15.8%), and epinephrine injection (14.0%). CONCLUSIONS The emergent DBE had the highest yields for diagnosis and therapy. The study finding showed a pivotal role of emergent DBE in overt SSBB.

Time-Series Analyses of Transcriptomes and Proteomes Reveal Molecular Networks Underlying Oil Accumulation in Canola.

Understanding the regulation of lipid metabolism is vital for genetic engineering of canola (Brassica napus L.) to increase oil yield or modify oil composition. We conducted time-series analyses of transcriptomes and proteomes to uncover the molecular networks associated with oil accumulation and dynamic changes in these networks in canola. The expression levels of genes and proteins were measured at 2, 4, 6, and 8 weeks after pollination (WAP). Our results show that the biosynthesis of fatty acids is a dominant cellular process from 2 to 6 WAP, while the degradation mainly happens after 6 WAP. We found that genes in almost every node of fatty acid synthesis pathway were significantly up-regulated during oil accumulation. Moreover, significant expression changes of two genes, acetyl-CoA carboxylase and acyl-ACP desaturase, were detected on both transcriptomic and proteomic levels. We confirmed the temporal expression patterns revealed by the transcriptomic analyses using quantitative real-time PCR experiments. The gene set association analysis show that the biosynthesis of fatty acids and unsaturated fatty acids are the most significant biological processes from 2-4 WAP and 4-6 WAP, respectively, which is consistent with the results of time-series analyses. These results not only provide insight into the mechanisms underlying lipid metabolism, but also reveal novel candidate genes that are worth further investigation for their values in the genetic engineering of canola.

Transfer of sclerotinia resistance from wild relative of Brassica oleracea into Brassica napus using a hexaploidy step.

KEY MESSAGE: Sclerotinia resistance was transferred into rapeseed from a wild relative of Brassica oleracea (B. incana) using hexaploids derived from crosses between B. incana and rapeseed as a bridge. A high level of resistance against Sclerotinia sclerotiorum has been documented in wild Brassica oleracea, but not in cultivated rapeseed (Brassica napus). To transfer sclerotinia resistance from a wild relative into rapeseed, a strategy was proposed using hexaploids (AACCCC) derived from crosses between the wild B. oleracea-related B. incana genotype 'C01' and the Chinese rapeseed variety 'Zhongshuang 9' as a bridge. Progenies (BC1F1) generated by backcrossing the hexaploid to 'Zhongshuang 9' could be generated with a high crossability (average 18.3 seeds per pod). Seventy-three individuals in BC1F1 were firstly screened for resistance with five molecular markers linked to the major resistance QTL on chromosome C09 in 'C01', and 11 individuals harboring resistance loci were selected to develop vegetative clones. Of these, five exhibited significantly higher resistance than 'Zhongshuang 9' and the most resistant individual was chosen to develop the BC1F2 progeny. Finally, five individual genotypes with nearly twofold higher resistance than 'Zhongshuang 9' were found among 100 BC1F2 individuals by using marker-assisted selection and resistance evaluation. Hereof, one rapeseed-type individual with 38 chromosomes and good self-fertility (15.0 ± 3.56 seeds/pod) was identified. Our results indicate that the proposed strategy is effective for transferring sclerotinia resistance from a wild relative of B. oleracea into rapeseed.

[Diagnosis of obscure gastrointestinal bleeding among different age groups by double balloon enteroscope].

OBJECTIVE: To investigate the diagnostic value of double balloon enteroscope (DBE) on obscure gastrointestinal bleeding(OGIB) and to analyze etiological characteristics among different age groups. METHODS: The clinical data of patients undergoing DBE due to OGIB in the Department of Gastroenterology in Renmin Hospital of Wuhan University from January 2007 to January 2012 were retrospectively analyzed and compared among different age groups. Patients were divided into the young group(age≤40, n=86), the middle age group(aged 41-59, n=81), and the elderly group (age≥60, n=49). The detection of bleeding origin by DBE was compared between different age groups. RESULTS: Diagnosis rates in young, middle age, elderly group were 83.7%(72/86), 87.7%(71/81), 81.6%(40/49) without statistical differences(P>0.05). Complication rates in the young, middle age, and elderly group were 1.2%(1/86), 2.5%(2/81), 2.0%(1/49) without statistic difference(P>0.05). The most common cause in young group was diverticulum/replica malformation while the most common location was ileum. The most common cause in both middle age and elderly group was tumor. CONCLUSIONS: DBE is an effective and safe method for diagnosis of OGIB among different age groups. Each age group has its etiological characteristics. Diagnosis and therapeutic strategy based on age-related characteristics is worthy of further investigation.

First prospective, population-based inflammatory bowel disease incidence study in mainland of China: the emergence of "western" disease.

BACKGROUND: Previously a disease of the West and rarely seen in China, inflammatory bowel disease (IBD) is now increasing in incidence in China. However, its true incidence is unknown. The incidence of IBD in Wuhan, a major city in central China, was investigated using population-based methods. METHODS: A prospective, population-based IBD incidence study was conducted between January 1, 2010, and December 31, 2010. New IBD cases were identified by gastroenterologists and from hospital case records in 17 central hospitals covering the health care service of central Wuhan. Cases were confirmed by follow-up and assessed by a specialist IBD group every 3 months. The population at risk was 6,085,556. RESULTS: Overall, 131 new cases of IBD were identified during the 1-year period, including 97 cases of ulcerative colitis (UC) and 34 cases of Crohn's disease (CD). The age-adjusted incidence for all IBD, UC, and CD were 1.96 per 100,000 (95% confidence interval [CI], 1.62-2.30 per 100,000), 1.45 (95% CI, 1.16-1.75), and 0.51 (95% CI, 0.33-0.68), respectively. CD affected the small bowel only in 15%, colon only in 24%, and ileocolonic in 61%. CD often presented with complicated phenotype: inflammatory (44%), stricturing (29%), and penetrating (24%). Among patients with UC, complications included proctitis (34.5%), left-sided colitis (44.6%), and extensive colitis (19.5%). CONCLUSIONS: There is a substantial incidence of IBD in China. Although still lower than in the West, the emergence of IBD will necessitate specific health care planning and education and offers the possibility of identifying causative factors in a population with a rapidly increasing incidence.

Clinical and endoscopic analysis of gastric Dieulafoy's lesion.

AIM: To investigate the incidence, location, clinical presentation, diagnosis and effectiveness of endoscopic treatment of gastric Dieulafoy's lesion (DL) in China. METHODS: All patients who received emergency upper gastrointestinal (GI) endoscopy due to gastric DL from February 2000 to August 2008 at GI endoscopy center of Renmin Hospital of Wuhan University were included in this study. The clinical presentation, medical history, location and characteristics of DL methods and effectiveness of therapy of patients with DL were retrospectively analysed by chart reviews. Long-term follow-up data were collected at outpatient clinics or telephone interviews. RESULTS: Fifteen patients were diagnosized with DL, which account for 1.04% of the source of bleeding in acute non-variceal upper GI bleeding. Common comorbidities were found in one patient with hypertension and diabetic mellitus. Hemoclip or combined therapy with hemoclip produced primary hemostasis in 92.8% (13/14) of patients. CONCLUSION: DL is uncommon but life-threatening in China. Hemoclip proved to be safe and effective in controlling bleeding from DL.

Risk factors for ulcerative colitis in a Chinese population: an age-matched and sex-matched case-control study.

BACKGROUND AND AIMS: Cigarette smoking, alcohol use, appendectomy, and family history of inflammatory bowel disease (IBD) have all been shown to be associated with IBD, but there were no reports of risk factors for IBD in a Chinese population in which the incidence of IBD is increasing during the past decade. We conducted a case-control study to examine associations between previously reported environmental risk factors and development of ulcerative colitis (UC) in Wuhan city, central China. METHODS: A total of 177 patients with UC and 177 age-matched and sex-matched controls were prospectively studied in Wuhan city from January 2004 to December 2004. An age-matched and sex-matched case-control study was conducted to assess the role of smoking, alcohol use, appendectomy, and other potential risk factors in the development of UC by a detailed questionnaire. RESULTS: Smoking was a protective factor and exsmoking is a risk factor for UC [compared with nonsmokers, smokers: odds ratios (OR)=0.28, 95% confidence intervals (CI): 0.16-0.48, P=0.0001; exsmokers: OR=4.36, 95%CI: 1.46-13.04, P=0.008]. Positive family history of IBD was a risk factor (OR=4.35, 95%CI: 1.21-15.71, P=0.025) whereas appendectomy was a protective factor (OR=0.24, 95%CI: 0.07-0.86, P=0.028) for UC. There were no significant associations between UC and other factors examined. CONCLUSIONS: Although the incidence of UC in Chinese is relatively lower than that in white, the same risk factors for UC that were reported in white populations were associated with Chinese UC patients. Specifically, smoking was a protective factor for UC and exsmoking was associated with an increase risk of UC in a Chinese population. Family history of IBD was shown to be a risk for UC, whereas appendectomy was associated with a low risk for UC.

Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, central China.

BACKGROUND: Inflammatory bowel disease (IBD) had been uncommon in China until about 1990, but since then, it has been seen in the clinical setting more and more. The prevalence and phenotype of IBD in the Chinese population is not well known. The present study investigates the trend of prevalence in ulcerative colitis (UC) and Crohn's disease (CD) in Wuhan City, central China, and evaluates clinical features, extraintestinal manifestations, and the treatment of IBD in the last 14 years. METHODS: Three hundred and eighty-nine patients with UC and 63 patients with CD were retrospectively collected from 5 central hospitals in Wuhan City, in which high-quality endoscopic and histological diagnoses were available from 1990 to 2003. UC and CD were diagnosed based on clinical, experimental, radiological, endoscopic, and histological examinations according to the internationally accepted Lennard-Jones criteria. RESULTS: The trend toward prevalence of UC and CD increased between 1990 and 2003 in Wuhan City. There was no change in the sex and age distribution comparing 1990 to 1996 with 1997 to 2003 both in UC and CD. However, the number of individuals with higher education and a professional occupation during 1997 to 2003 was significantly higher than that during the period 1990 to 1996 in patients with UC (OR 2.1, 95% CI 1.27-3.35, P = 0.004; OR 2.2, 95% CI 1.31-3.61, P = 0.003). The mean age of patients with CD was significantly younger than that of UC at the time of diagnosis (32.6 +/- 12.5 vs. 42 +/- 14.5, P < 0.0001). The ratio of male to female patients was 1.53:1 in UC and 2.32:1 in CD, respectively. The mean duration of onset of the disease to diagnosis was 1.4 years in UC and 1.1 years in CD. The extra intestinal manifestations of UC and CD were 5.7% and 19%, respectively, and complications of UC and CD were 6.4% and 50.8%, respectively. Only 3% of UC patients required surgery, whereas 27% of CD patients underwent surgical procedures (P < 0.001). CONCLUSION: The prevalence of IBD has increased in Wuhan City, central China, but is not as high as in Western countries. The disease in Wuhan City has often been associated with young adult professional males with a high level of education. The clinical presentation of UC was often mild and had few extra intestinal manifestations.

[Influence of sodium butyrate on growth of HT-29 colon carcinoma cells and expression of inducible nitric oxide synthase (iNOS)].

BACKGROUND & OBJECTIVE: Sodium butyrate could inhibit several cancer cell lines in vitro. This study was designed to investigate the effects of sodium butyrate on the growth of HT-29 colon carcinoma cells, the expression of iNOS, and the excretion of NO. METHODS: The HT-29 cells were co-incubated with sodium butyrate at various concentration. The cell proliferation was determined by MTT test, and the iNOS protein of HT-29 cells was stained by immunochemical SP method. The absorbance value (A value) of iNOS was measured by automatic image analysis system. Griess's technique was used to examine the excretion of nitric oxide (NO). RESULTS: The survival rates of HT-29 cells treated by sodium butyrate decreased in a time-dependent and dose-dependent manner. IC(50) value of sodium butyrate was decreased with prolonged incubation time (15.4 mmol/L at 12 hours, 5.7 mmol/L at 24 hours, 2.5 mmol/L at 36 hours, 0.9 mmol/L at 48 hours). Simultaneously sodium butyrate decreased the expression of iNOS in the cytoplasm and the excretion of NO in a similar manner. CONCLUSION: Sodium butyrate could inhibit the expression of iNOS, consequently reduce the excretion of NO. It may play an important role in the mechanism that sodium butyrate inhibits the growth of HT-29 colon carcinoma cells.