Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.

BACKGROUND: The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets. METHODS: The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed. RESULTS: Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy. CONCLUSIONS: WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.

High FNDC1 expression correlates with poor prognosis in gastric cancer.

Gastric cancer is a common human cancer worldwide. Fibronectin is an important extracellular matrix protein that has been implicated in many cancers and is known to be associated with proliferation and migration. Fibronectin type III domain containing 1 (FNDC1) contains a major component of the structural domain of fibronectin. The objectives of the present study were to measure FNDC1 expression in gastric cancer tissues and evaluate its value as a potential prognostic marker for gastric cancer. FNDC1 protein expression was analyzed by immunohistochemistry in 98 samples of gastric cancer tissue and 25 adjacent normal tissues. The associations between FNDC1 level and various clinicopathological characteristics were assessed, and the correlation between FNDC1 expression levels and prognosis of patients with gastric cancer was analyzed using a Kaplan-Meier analysis. It was demonstrated that FNDC1 expression in gastric cancer tissues and adjacent tissues was significantly different. FNDC1 expression levels were significantly higher in gastric cancer tissues compared with normal gastric tissues (P<0.001). Among the clinicopathological characteristics evaluated, clinical stage (P<0.001), T classification (P<0.001), N classification (P<0.001) and pathological differentiation (P=0.044) were significantly associated with high FNDC1 expression. Higher FNDC1 expression level was significantly correlated with poorer survival. The present findings suggest that FNDC1 expression levels may be a promising prognostic biomarker for gastric cancer.

[Value of endoscopic ultrasound-guided fine needle aspiration in pretest prediction and diagnosis of pancreatic ductal adenocarcinoma].

OBJECTIVE: To identify the predictive factors for differentiating pancreatic ductal adenocarcinoma (PDAC) from other neoplastic solid pancreatic lesions and assess the accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis of PDAC. METHODS: We retrospectively analyzed the clinical data of patients referred for EUS-FNA evaluation of pancreatic lesions in the Digestive Endoscopic Center of Nanfang Hospital between January, 2009 and May, 2016. The cases with unknown diagnosis, missing data, repeated punctures, cystic lesions and benign lesions were excluded from the analysis. The positivity rates of EUS-FNA were compared between patients with PDAC and those with non-PDAC lesions, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS-FNA were assessed in the diagnosis of PDAC. Univariate and multivariate logistic regression analyses were used to identify the factors for differentiating PDAC from non-PDAC lesions based on the demographic characteristics, clinical presentations, laboratory data, and endoscopic ultrasonography imaging features of the patients. RESULTS: Among the 75 patients with solid neoplastic pancreatic lesions, 54 (72.0%) were found to have PDAC and 21 (28.0%) had non-PDAC lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA for the diagnosis of PDAC were 77.8%, 100.0%, 100.0%, 63.6% and 84.0%, respectively. No significant difference was found in the positivity rate of EUS-FNA between patients with PDAC and those with non-PDAC lesions (77.8% vs 76.2%, P > 0.05). Multivariate regression analysis identified abdominal pain (OR=5.163, 95%CI: 1.093-24.389, P=0.038), lesion size (OR=0.926, 95%CI: 0.877-0.978, P=0.006), characteristics of the solid lesions (OR=7.105, 95%CI: 1.440-35.043, P=0.016), and evidence of metastases (OR=6.165, 95%CI: 1.332-28.533, P=0.020) as the independent factors for predicting PDAC. CONCLUSIONS: The pretest characteristics including abdominal pain, evidence of metastases, and lesion size and lesion characteristics defined by endoscopic ultrasonography findings can reliably predict a diagnosis of PDAC. EUS-FNA has a high sensitivity and a high specificity for the diagnosis of PDAC.

[Comparison of risk factors for serrated polyps and conventional adenoma and the suitable age to start colorectal cancer screening].

OBJECTIVE: To compare the risk factors associated with serrated polyps (SPs) and conventional adenoma (CA). METHODS: One hundred and three healthy control subjects, 100 patients with pathologically confirmed SPs and 115 with CA were randomly selected from individuals undergoing colonoscopy in Nanfang Hospital from 2012 to 2015. The demographic and clinical data were collected from the subjects, including age, gender, height, weight, hypertension, diabetes, smoking status, alcohol use, family history of colorectal cancer (CRC) and blood lipids. RESULTS: Among the enrolled subjects, the mean onset age of SPs was 48.87 years (95%CI: 47.22-50.52 years), significantly younger than that of CA (P%0.038). The risk factors both for SPs and CA include an advanced age, a male gender (OR%2.75 [95%CI: 1.50-5.07] for SPs, and OR%2.19 [95%CI: 1.22-3.95] for CA), and a high body mass index (OR%1.18 [95%CI: 1.06-1.30] for SPs and OR%1.20 [95%CI: 1.09-1.32] for CA. Relative to the young individuals (below 45 years of age), the middle-aged individuals (45-60 years of age) had increased risks for SPs and CA by 2.31 [95% CI: 1.46-3.65] folds and 4.10 [95%CI: 2.50-6.72] folds, respectively, and in the elderly (beyond 60 years of age), the risks further increased by 2.77 [95%CI: 1.52-5.04] folds for SPs and by 6.00 [95%CI: 3.26-11.05] folds for CA. Age was more strongly associated with CA than with SPs (OR%2.14 [95%CI: 1.21-3.78], the elderly vs the young, P%0.009). CONCLUSION: SPs and CA have common risk factors, thus the screening strategy for CA may also be applicable to SPs. As the mean onset age of SPs is earlier than 50 years and SPs may rapidly progress to a carcinogenic state, an earlier screening age needs to be considered.

[Expressions of inflammatory cytokines in intestinal mucosa and their prognostic value in patients with ulcerative colitis].

OBJECTIVE: To detect the expressions of IL-17, IL-23, IL-22 and IL-11 in the intestinal mucosa of patients with ulcerative colitis (UC) and analyze their prognostic values. METHODS: Forty patients with active UC, 15 with UC in remission and 15 healthy subjects were examined for the expressions and distribution of IL-17, IL-23, IL-22, and IL-11 in the colorectal mucosausing immunohistochemistry. We further collected the data from 40 patients with routine therapy and regular follow-up and compared the expressions of those cytokines according to the condition of mucosal healing. RESULTS: The expressions of cytokines in patients with active UC were significantly higher than those in patients with remittent UC and healthy control subjects (IL-17: 0.0727∓0.0037 vs 0.0354∓0.0243 vs 0.0330∓0.0045; IL-23: 0.1407∓0.0068 vs 0.0865∓0.0051 vs 0.0442∓0.0137; IL-22: 0.0522∓0.0045 vs 0.0259∓0.0063 vs 0.0115∓0.0061; IL-11: 0.0479∓0.0022 vs 0.0365∓0.0024 vs 0.0232∓0.0009, P<0.05). The expression levels of IL-17, IL-23, and IL-22 increased significantly with the increase of the disease activity (IL-17: 0.0545∓0.0072 vs 0.0786∓ 0.0051 vs 0.0847∓0.0197; IL-23: 0.1112∓0.0046 vs 0.1480∓0.0089 vs 0.1644∓0.0190; IL-22: 0.0307∓0.0063 vs 0.0548∓ 0.0071 vs 0.0719∓0.0056, P<0.05). In patients with active UC, the expression levels of the 4 cytokines in the intestinal mucosa were positively correlated with the endoscopic activity grade (P<0.05), and IL-17 and IL-22 expression levels were also positively correlated with the histological grade (P<0.05). All the 4 cytokines were positively intercorrelated. The patients with low IL-17 expression (25.00%) showed a significantly lower rate of poor mucosal healing than those with high IL-17 expressions (25% vs 67%, P<0.05). CONCLUSION: The cytokines IL-17, IL-23, IL-22, and IL-11 all participate in the pathogenesis of UC and may serve as indicators for evaluating the inflammatory activity. The expression level of IL-17 can be a valuable indicator for predicting mucosal healing in UC patients after a short-term treatment.

GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells.

AIM: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells. METHODS: The mRNA expression of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), adiponectin, leptin, resistin, adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and the long isoform of leptin receptor (OB-Rb) and protein levels of adiponectin, leptin, and resistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay, respectively, on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064. Moreover, mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0, 12, 24, and 48 h in HepG2 cells treated with GW4064. RESULTS: The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, resistin, AdipoR1, AdipoR2, and OB-Rb and protein levels of adiponectin, leptin, and resistin increased along with differentiation of 3T3-L1 preadipocytes (P < 0.05 for all). The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, and AdipoR2 in 3T3-L1 preadipocytes, and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064, when compared with the control group (P < 0.05 for all). A similar trend was observed for protein levels of adipokines (including adiponectin, leptin and resistin). However, the expression of resistin, AdipoR1, and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064. CONCLUSION: The FXR agonist through regulating, at least partially, the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.

Interleukin-11 induces the expression of matrix metalloproteinase 13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways.

Interleukin (IL)-11 is expressed in the majority of gastric carcinomas and has been associated with an aggressive phenotype and poor prognosis of gastric adenocarcinoma. Matrix metalloproteinase (MMP)-13 has been detected in numerous invasive malignant tumor types and exhibits a broad spectrum of activities on connective tissue components. In this study, we investigated whether IL-11 affects the expression of MMP-13 in human gastric cancer cells, as well as the underlying mechanism. Using western blot assays, we investigated the effect of recombinant human (rh) IL-11 on the expression of MMP-13 in gastric carcinoma cell lines. Using the PI3K inhibitor wortmannin and RNA interference to target the STAT3 gene, we investigated the effects of PI3K inhibition and/or STAT3 depletion on the expression of the MMP-13 protein. Results showed that IL-11 induced MMP-13 expression in a time- and concentration-dependent manner in SCH cells. IL-11 activated PI3K-AKT and JAK-STAT3 signal transduction. Wortmannin and depletion of STAT3 by means of small interfering RNA (siRNA) synergistically reduced the expression of MMP-13. These findings suggested that IL-11 induces the expression of MMP-13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways.

ZNF703 acts as an oncogene that promotes progression in gastric cancer.

ZNF703, a member of the NET/Nlz family of zinc finger transcription factors, contributes to aspects of developmental growth and patterning across evolutionarily diverse species. ZNF703 has been identified as a novel oncogene in human breast cancer. In the present study, we investigated the expression of ZNF703 in gastric carcinoma and attempted to determine, using cell line models, its biological actions. Using immunohistochemistry, we analyzed the ZNF703 protein expression in 120 clinicopathologically characterized gastric cancer cases. Using RNA interference, we investigated the effects of ZNF703 depletion on tumor proliferation and metastasis in vitro. We found that ZNF703 was overexpressed in invasive gastric carcinoma tissues, and its expression levels were closely correlated with the depth of invasion, node metastasis and venous invasion. RNA interference-mediated silencing of the ZNF703 gene in SGC7901 cells inhibited cell proliferation and migration significantly. The results showed that ZNF703 acts as a gastric cancer oncogene and should be considered a therapeutic target for metastatic gastric cancer.

[Effects of farnesoid X receptor agonist on adiponectin and its receptors].

OBJECTIVE: To investigate the effects of GW4064, a farnesoid X receptor (FXR) agonist, on adiponectin and its receptors during the differentiation of 3T3-L1 preadipocytes and on adiponectin receptors in HepG2 cells. METHODS: The mRNA expressions of FXR, PPARγ2, adiponectin, AdipoR1, and AdipoR2 and the protein levels of adiponectin on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes treated with GW4064 were detected by fluorescent real-time PCR and ELISA, respectively. The mRNA expressions of AdipoR1 and AdipoR2 in HepG2 cells were also examined at 0, 12, 24, and 48 h after GW4064 treatment. RESULTS: The mRNA expressions of FXR, PPARγ2, adiponectin, and AdipoR2 in 3T3-L1 preadipocytes and AdipoR2 in HepG2 cells treated with GW4064 was significantly increased compared with the control group (all P<0.05). The protein level of adiponectin was also significantly increased after GW4064 treatment. The expression of AdipoR1 in either 3T3-L1 preadipocytes or HepG2 cells showed no significant changes after GW4064 treatment. CONCLUSION: GW4064 can up-regulate the expressions of FXR, PPARγ2, adiponectin, AdipoR2 in 3T3-L1 preadipocytes and AdipoR2 in HepG2 cells. As adiponectin and its receptors are two important factors in the treatment of non-alcoholic fatty liver disease, FXR agonist may potentially produce therapeutic effect on non-alcoholic fatty liver disease and can regulate adipocytes via up-regulating PPARγ during adipocyte differentiation.