Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis.

BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD. PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile. METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT). RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism. CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.

A Potential Nine-lncRNAs Signature Identification and Nomogram Diagnostic Model Establishment for Papillary Thyroid Cancer.

The purpose of our current study was to establish a long non-coding RNA(lncRNA) signature and assess its prognostic and diagnostic power in papillary thyroid cancer (PTC). LncRNA expression profiles were obtained from the Cancer Genome Atlas (TCGA). The key module and hub lncRNAs related to PTC were determined by weighted gene co-expression network analysis (WGCNA) and LASSO Cox regression analyses, respectively. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis were implemented to analyze the possible biological processes and signaling pathways of hub lncRNAs. Associations between key lncRNA expressions and tumor-infiltrating immune cells were identified using the TIMER website, and proportions of immune cells in high/low risk score groups were compared. Kaplan-Meier Plotter was used to evaluate the prognostic significance of hub genes in PTC. A diagnostic model was conducted with logistic regression analysis, and its diagnostic performance was assessed by calibration/receiver operating characteristic curves and principal component analysis. A nine-lncRNAs signature (SLC12A5-AS1, LINC02028, KIZ-AS1, LINC02019, LINC01877, LINC01444, LINC01176, LINC01290, and LINC00581) was established in PTC, which has significant diagnostic and prognostic power. Functional enrichment analyses elucidated the regulatory mechanism of the nine-lncRNAs signature in the development of PTC. This signature and expressions of nine hub lncRNAs were correlated with the distributions of tumor infiltrating immune cells. A diagnostic nomogram was also established for PTC. By comparing with the published models with less than or equal to nine lncRNAs, our signature showed a preferable performace for prognosis prediction. In conclusion, our present research established an innovative nine-lncRNAs signature and a six-lncRNAs nomogram that might act as a potential indicator for PTC prognosis and diagnosis, which could be conducive to the PTC treatment.

StMBF1c positively regulates disease resistance to Ralstonia solanacearum via it's primary and secondary upregulation combining expression of StTPS5 and resistance marker genes in potato.

Multiprotein bridging factor 1 (MBF1) is a transcription coactivator that has a general defense response to pathogens. However, the regulatory mechanisms of MBF1 resistance bacterial wilt remain largely unknown. Here, the role of StMBF1c in potato resistance to Ralstonia solanacearum infection was characterized. qRT-PCR assays indicated that StMBF1c could was elicited by SA, MJ and ABA and the time-course expression pattern of the StMBF1c gene induced by R. solanacearum was found to be twice significant upregulated expression during the early and middle stages of bacterial wilt. Combined with the co-expression analysis of disease-resistant marker genes, gain-of-function and loss-of-function assays demonstrated that StMBF1c was associated with defence priming. Overexpression or silencing the MBF1c could enhance plants resistance or sensitivity to R. solanacearum through inducing or reducing NPR and PR genes related to SA signal pathway. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiment results confirmed the interaction of StMBF1c with StTPS5 which played a key role in ABA signal pathway in potato. It is speculated that by combining StTPS5 and resistance marker genes, StMBF1c is activated twice to participate in potato bacterial wilt resistance, in which EPI, PTI involved.

Modulation of gut microbiota and intestinal barrier function during alleviation of antibiotic-associated diarrhea with Rhizoma Zingiber officinale (Ginger) extract.

Antibiotic-associated diarrhea (AAD) is typically mediated by antibiotic therapy, which has increased in prevalence in recent years. Previous studies have suggested that ginger, a common spice and herbal medicine, can modulate the composition of gut microbiota and is beneficial against gastrointestinal disease. This study investigates the therapeutic effects of fresh ginger extract on AAD in a rat model. Gut microbiota and intestinal barrier function were also studied. Ginger was administered to rats with AAD. Diarrhea symptoms were assessed, and 16s rRNA sequencing analysis of gut microbiota was performed. An AAD model was successfully established, and ginger was found to effectively ameliorate AAD-related diarrhea symptoms. After the intervention of ginger decoction, the diversity (rather than richness) of gut microbiota was significantly improved, and the gut microbiota recovery was accelerated. At the genus level, Escherichia_Shigella and Bacteroides levels decreased and increased the most, respectively. Additionally, these changes were demonstrated to be coincidental with the moderate restoration of intestinal barrier function, especially the restoration of tight junction protein ZO-1. Our data indicate that ginger could restore gut microbiota and intestinal barrier function during alleviation of AAD.

Comparison of Early Submucosal Enhancement and Tumor Stalk in Staging Bladder Urothelial Carcinoma.

OBJECTIVE: The purpose of this study was to compare the efficacy of submucosal enhancement on dynamic contrast-enhanced MRI (DCE-MRI) and detection of a stalk on DWI for differentiating stage T1 from stage T2 bladder urothelial carcinoma. SUBJECTS AND METHODS: Our prospective study was approved by the institutional medical ethics committee and informed consent was obtained from all patients. Fifty-nine patients (92 tumors in total) with urothelial bladder cancer underwent MRI within 2 weeks before surgery. Two image sets of T2-weighted MRI with DWI and T2-weighted with DCE-MRI were interpreted independently at 2-week intervals by two uroradiologists without any knowledge of the surgical or histologic findings. The tumor was categorized as stage T1 or lower when a stalk was evident at the tumor base on DWI or when continuous linear submucosal enhancement was detected in the early phase of DCE-MRI. Tumors without stalks or with discontinuous linear submucosal enhancement were categorized as stage T2. RESULTS: Of the 42 tumors with stalks on DWI, 41 showed continuous and one had discontinuous submucosal enhancement on DCE-MRI. In 50 carcinomas without stalks on DWI, submucosal enhancement was absent in 34, continuous in 12, and discontinuous in four. The staging accuracy of DWI (91.3%, 84/92) and DCE-MRI (91.3%, 84/92) was improved to 94.6% (87/92) by combining the interpretations of both DWI and DCE-MRI. CONCLUSION: Submucosal linear enhancement under the tumor base on DCE-MRI complements tumor stalk detection on DWI for differentiating stage T1 from stage T2 bladder urothelial carcinoma.

[Diagnostic value of high-field MRI for Peyronie's disease].

OBJECTIVE: To analyze the MRI manifestations of Peyronie's disease and investigate the value of high-field MRI in the diagnosis of the disease. METHODS: Using a small surface coil, we performed 3.0 Tesla MRI for 14 patients with clinically diagnosed Peyronie's disease. The MRI protocol included routine sequences (T1WI, T2WI, and enhanced T1WI) and susceptibility-weighted imaging (SWI). Each patient had received 2－4 penile ultrasound examinations previously. We compared the MRI findings with the results of ultrasonography. RESULTS: MRI manifested 25 penile plaques in the 14 patients, 3 (7 plaques) with inflammation, 4 (8 plaques) with fibrosis, and the other 7 (10 plaques) with calcification displaying a low signal intensity on SWI. Ultrasonography had revealed the 10 calcified plaques in all the 20 examinations, but exhibited the 7 inflammatory and 8 fibrotic ones in only 3 of the 23 examinations. The combination of MRI SWI sequences was necessitated for the detection of calcified plaques and achieved higher detection rates than ultrasonography for inflammatory and fibrotic plaques (P<0.05). CONCLUSIONS: High-field MRI has high sensitivity and accuracy in the diagnosis of Peyronie's disease, which can effectively display penile plaques of different nature in the early stage through multi-parametric sequences.

Expression of Pax8 is decreased and bortezomib does not increase the iodine uptake in thyroid carcinoma cells.

Fundamental treatment for papillary thyroid carcinoma (PTC) involves total or subtotal thyroidectomy. Iodine-131 ((131)I) is routinely utilized to target remnant thyroid cancer and metastasis after thyroidectomy. The effectiveness of other therapeutic modalities remains unsatisfactory; thus, these patients have a poor prognosis. The manner in which the ability of (131)I uptake can be improved is vital for their prognosis. Bortezomib has been used as a re-differentiation agent for the treatment of patients with multiple myeloma; however, little is reported about the role of bortezomib in thyroid cancer. To evaluate the therapeutic potential of bortezomib in a human PTC cell line, expression of paired-box 8 (Pax8) protein was determined using Western blot in PTC, normal thyroid, and anaplastic/undifferentiated thyroid carcinoma (ATC) cells. The expression of Pax8 protein in PTC cells pretreated with bortezomib was determined using the same method. Iodine uptake was determined using (131)I radioactivity assay. The level of Pax8 protein in normal thyroid cells was significantly higher than in PTC (P < 0.05) and ATC cells (P < 0.05); its expression in PTC cells was also significantly higher than in ATC cells (P < 0.05). The PTC cells in the bortezomib-treated group showed a higher expression of Pax8 protein than the control group (P < 0.05). These findings indicate that bortezomib can increase the expression of Pax8, but does not significantly increase the iodine uptake of PTC cells.

Methylation of sodium iodide symporter promoter correlated with aggressiveness and metastasis in papillary thyroid carcinoma: a meta-analysis.

BACKGROUND: Methylation of sodium iodide symporter promoter has been reported to increase the incidence of papillary thyroid carcinoma (PTC). In this meta-analysis stratified via methylation of sodium iodide symporter promoter, we evaluate the relationship between methylation of sodium iodide symporter promoter and PTC. The association between methylation with aggressiveness and metastasis potential of PTC is also discussed. METHODS: We searched electronic databases for original articles and references of included studies both in English and Chinese from 1966 to 2014. Two reviewers selected the case-control study and extracted data from relevant literature independently. RESULTS: Seven articles, including 360 cases and 268 controls, were involved in this meta-analysis. The prevalence of PTC in patients with methylated sodium iodide symporter promoter was significantly higher than those with non-methylated promoter (OR=7.36, 95% CI: 4.25-12.74, P<0.001). Stratified analysis showed that PTC patients with multiple lesions, capsule invasion and lymphatic metastasis had significantly higher rates of methylation (OR=2.22, 95% CI: 1.12-4.41, P=0.02; OR=2.14, 95% CI: 1.12-4.08, P=0.02; OR=3.56, 95% CI: 1.97-6.46, P<0.0001). But no relationship was found among the methylation of sodium iodide symporter and age, gender and size of tumor. CONCLUSIONS: The methylation of sodium iodide symporter promoter is related with PTC and its aggressive and metastatic potential. Due to the limited sample size, more clinical researches should be taken in the future.

Multiparametric 3-T MRI for differentiating low-versus high-grade and category T1 versus T2 bladder urothelial carcinoma.

OBJECTIVE. The purpose of this study was to determine an optimal multiparametric MRI protocol for characterizing tumors of low versus high grade and differentiating tumors as T1 versus T2 for preoperative staging of bladder urothelial carcinoma. SUBJECTS AND METHODS. Thirty-nine patients underwent MRI within 1 week before surgery. Three image sets-T2-weighted plus diffusion-weighted MRI (DWI), T2-weighted plus dynamic contrast-enhanced MRI (DCE-MRI), and T2-weighted plus DCEMRI plus DWI-were independently interpreted by two readers at 2-week intervals. ROC curves were plotted for both readers to compare the diagnostic efficacy of the three sets for detrusor muscle invasion for each reader, and the areas under the ROC curve were compared by use of the Bonferroni test. The apparent diffusion coefficient (ADC) values were correlated with histopathologic grade. RESULTS. A total of 49 category T1 and T2 lesions were analyzed. The average ADC of 11 low-grade tumors (1.141 ± 0.164 × 10(-3) mm(2)/s) was significantly (p < 0.05) higher than that of 20 high-grade malignant tumors (0.766 ± 0.091 × 10(-3) mm(2)/s). Neither reader considered T1 tumors as probably having muscle invasion (category T2) in the T2-weighted plus DWI image sets or the T2-weighted plus DWI plus DCE-MRI image sets. Using the T2-weighted plus DCE-MRI sets, the two readers overstaged 13 and 15 of 36 tumors by misdiagnosing category T1 as T2. With the cutoff ADC value of 0.899 × 10-3 mm(2)/s, the sensitivity and specificity for differentiating high- and low-grade bladder urothelial carcinoma were 100% and 95%. CONCLUSION. Multiparametric MRI with T2-weighted plus DWI plus DCE technique is the optimal protocol for preoperative staging of organ-confined bladder urothelial carcinoma. The ADC of low-grade tumors is significantly higher than that of high-grade tumors with 100% sensitivity and 95% specificity at a cutoff ADC value of 0.899 mm(2)/s.

MR diffusion tensor imaging of normal kidneys.

PURPOSE: To assess the feasibility of diffusion tensor imaging (DTI) of normal kidneys and the influence of hydration state. MATERIALS AND METHODS: Ten healthy volunteers underwent renal DTI after fasting for 12 hours and 4 hours, without fasting, and following water diuresis. Medullary and cortical apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured and compared in the four different states of hydration. DTI was performed with a 3T magnetic resonance imaging (MRI) system using fat-saturated single-shot spin-echo echo planar imaging sequence. RESULTS: ADC of normal cortex (2.387 ± 0.081 × 10(-3) mm(2) /s) was significantly higher (t = 20.126, P = 0) than that of medulla (1.990 ± 0.063 × 10(-3) mm(2) /s). The FA value of normal cortex (0.282 ± 0.017) was significantly lower (t = -42.713, P = 0) than that of medulla (0.447 ± 0.022). The ADC and FA values of the left renal cortex (2.404 ± 0.082 × 10(-3) mm(2) /s, 0.282 ± 0.017) and medulla (2.002 ± 0.081 × 10(-3) mm(2) /s, 0.452 ± 0.024) were not significantly different (P > 0.05) from those of right renal cortex (2.369 ± 0.080 × 10(-3) mm(2) /s, 0.283 ± 0.018) and medulla (1.978 ± 0.039 × 10(-3) mm(2) /s, 0.443 ± 0.019). Values for ADC (×10(-3) mm(2) /s) and FA in the 12-hour fasting, 4-hour fasting, nonfasting, and water diuresis states were 2.372 ± 0.095 and 0.278 ± 0.018, 2.387 ± 0.081 and 0.282 ± 0.017, 2.416 ± 0.051 and 0.279 ± 0.023, 2.421 ± 0.068, and 0.270 ± 0.021, respectively, in cortex, 1.972 ± 0.084 and 0.438 ± 0.014, 1.990 ± 0.063 and 0.447 ± 0.022, 2.021 ± 0.081 and 0.450 ± 0.031, 2.016 ± 0.076 and 0.449 ± 0.028, respectively, in medulla. The ADC and FA values in different hydration states were not significantly different (P > 0.05). CONCLUSION: DTI of normal kidneys is feasible with reproducible ADC and FA values independent of hydration states.

3T magnetic resonance diffusion tensor imaging in chronic kidney disease.

OBJECTIVE: To investigate the relationship of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with renal function on 3T diffusion tensor imaging (DTI) in chronic kidney disease. MATERIALS AND METHODS: Twenty healthy volunteers and 29 patients with CKD underwent DTI. The relationship among ADC, FA, and renal function was analyzed. RESULTS: Cortical and medullary ADC and FA values of patients with chronic kidney disease were lower than those of healthy volunteers (P = 0.000). Both the renal ADC and FA values correlated inversely with serum creatinine and blood urea nitrogen (P < 0.05). CONCLUSION: DTI is a feasible and non-invasive means to reflect the severity of renal function damaged.

Diffusion-weighted MRI in bladder carcinoma: the differentiation between tumor recurrence and benign changes after resection.

PURPOSE: To investigate the efficacy of diffusion-weighted MRI (DWI) in differentiating recurrent tumor from chronic inflammation and fibrosis after cystectomy or transurethral resection of bladder cancer. METHODS: Eleven patients with suspected tumor recurrence underwent pelvic DWI and dynamic contrast-enhanced (DCE) MRI at 3 months to 7 years following bladder cancer resection. The diagnosis was histologically confirmed in all patients by transurethral or cystoscopic resection of 27 lesions within 2 weeks of MR examinations. RESULTS: The accuracies, sensitivities, specificities, and positive predict values of DWI (92.6%, 100%, 81.8%, and 88.9%) were higher than those of DCE MRI (59.3%, 81.3%, 27.3%, and 54.2%) for detecting recurrent tumors. Using receiver operating characteristic analysis, the accuracy of DWI was significantly higher than that of DCE MRI (P < 0.05). There was no significant difference between DWI diagnosis and histopathology (P > 0.05), whereas the difference between diagnosis of DCE MRI and histopathology was significant (P < 0.05). The normalized apparent diffusion coefficients of recurrent tumors (0.697 ± 0.219) were significantly (P < 0.05) lower than those of postoperative inflammation or fibrosis (1.019 ± 0.143). CONCLUSIONS: DWI is superior to DCE MRI for differentiating recurrent bladder tumors from postoperative inflammation or fibrosis. DWI can be included in the follow-up MRI protocol after bladder cancer surgery.

[Influences of nevirapine on cell proliferation and expression of sodium/iodide symporter in human anaplastic thyroid carcinoma cell line].

OBJECTIVE: To explore the effects of nevirapine on the proliferation and expression of sodium-iodide symporter (NIS) mRNA in FRO cells in vitro. METHODS: The cells were incubated in different concentrations of nevirapine to evaluate the cell growth rate. And the expressions of NIS mRNA and TSHR mRNA were determined by real-time quantitative reverse polymerase chain reaction. RESULTS: Cell proliferation was inhibited after a 96 h nevirapine treatment. After incubating in the presence of 200 and 350 µmol/L nevirapine, the expression of NIS mRNA was (1.39 ± 0.04) and (1.85 ± 0.28) times versus the control cells (P < 0.01) while the expressions of TSHR mRNA was (2.23 ± 1.47) and (2.83 ± 0.78) times versus the control cells respectively (both P < 0.05). CONCLUSION: Nevirapine inhibits cell proliferation in FRO cell line. More importantly, the cells exposed to nevirapine may induce the up-regulations of NIS mRNA and TSHR mRNA.