Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.

BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women. OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy. METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated. RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model. CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.

Benign prostatic hyperplasia associated with white matter hyperintensities in men.

PURPOSE: Benign prostatic hyperplasia (BPH) describes common noncancerous prostate enlargement. BPH is usually associated with lower urinary tract symptoms and an increased risk of cerebrovascular diseases, such as stroke and its recurrence. White matter hyperintensities (WMHs), markers of cerebral injury, increase the risk of stroke, cognitive impairment, dementia, and death. The relationship between BPH and WMHs remains unclear. This study aimed to determine the association between BPH and WMHs. METHODS: A total of 788 male patients from the First Affiliated Hospital of Kunming Medical University from July 2019 to September 2021 were enrolled in this cross-sectional study. BPH was assessed by abdominal ultrasound, and three independent neuroradiologists rated the presence or absence of WMHs. Multiple imputations of chained equations were used to handle missing data. Logistic regression was used to assess the relationship between BPH and WMHs. RESULTS: Patients with BPH presented an increased risk of WMHs with a crude odds ratio (OR) of 2.76 (95% CI, 2.02-3.79) and an adjusted OR of 1.75 (95% CI, 1.24-2.48) after controlling for potential confounding factors in the multivariate logistic regression. CONCLUSION: We found that BPH was closely associated with WMHs in male Chinese individuals.

Electrochemical skin conductance and heart rate variability in patients with non-dialysis chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is very common now and associates with high overall and cardiovascular mortality. Numerous studies have reported that Heart rate variability (HRV) could also be used to detect cardiovascular autonomic dysfunction (CAD). We investigated the association of electrochemical skin conductance (ESC) of EZSCAN results with HRV in non-dialysis CKD patients. METHODS: In a cross-sectional study, we enrolled 248 prevalent non-dialysis CKD patients. Patients underwent a 24-h Holter (CB-2302-A, Bio Instrument, China). A time domain analysis of HRV was performed, and the following parameters were obtained: SDNN, SDANN, rMSSD, pNN50. EZSCAN device (Impeto Medical, Paris, France) measures ESC values of each participants. Mean global skin conductance computed as 0.5 * (reflecting (right + left hand)/2 + (right and left foot)/2). Log transforms data into a normal distribution for statistical analysis. RESULTS: There were 142 males and 106 females included in the present study. Patients' age was 56.6±17.08 years. Logarithm(Log) (global ESC) was independently predicted by age (P<0.01), hypertension history, estimated Glomerular filtration rate (eGFR) and log SDNN (P<0.05). While log SDANN, rMSSD and pNN50 were not independent predictors for log (global ESC). CONCLUSION: Increased global ESC significantly associated with elevated HRV, specifically SDNN in non-dialysis CKD patients. This suggested that global ESC may appear to be an important predictor of CAD, and even could be used as a cardiovascular risk factor in non-dialysis CKD patients.

Predicting anaplastic lymphoma kinase rearrangement status in patients with non-small cell lung cancer using a machine learning algorithm that combines clinical features and CT images.

Purpose: To develop an appropriate machine learning model for predicting anaplastic lymphoma kinase (ALK) rearrangement status in non-small cell lung cancer (NSCLC) patients using computed tomography (CT) images and clinical features. Method and materials: This study included 193 patients with NSCLC (154 in the training cohort, 39 in the validation cohort), 68 of whom tested positive for ALK rearrangements and 125 of whom tested negative. From the nonenhanced CT scans, 157 radiomic characteristics were extracted, and 8 clinical features were collected. Five machine learning (ML) models were assessed to find the best classification model for predicting ALK rearrangement status. A radiomic signature was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. The predictive performance of the models based on radiomic features, clinical features, and their combination was assessed by receiver operating characteristic (ROC) curves. Results: The support vector machine (SVM) model had the highest AUC of 0.914 for classification. The clinical features model had an AUC=0.805 (95% CI 0.731-0.877) and an AUC=0.735 (95% CI 0.566-0.863) in the training and validation cohorts, respectively. The CT image-based ML model had an AUC=0.953 (95% CI 0.913-1.0) in the training cohort and an AUC=0.890 (95% CI 0.778-0.971) in the validation cohort. For predicting ALK rearrangement status, the ML model based on CT images and clinical features performed better than the model based on only clinical information or CT images, with an AUC of 0.965 (95% CI 0.826-0.882) in the primary cohort and an AUC of 0.914 (95% CI 0.804-0.893) in the validation cohort. Conclusion: Our findings revealed that ALK rearrangement status could be accurately predicted using an ML-based classification model based on CT images and clinical data.

Glomerular filtration Rate, urine Albumin/ creatinine ratio and current perception threshold in patients with diabetic kidney disease.

BACKGROUND: Diabetic microvascular complications, including diabetic kidney disease (DKD), retinopathy (DR), and neuropathy (DN), were major causes of morbidity and mortality in diabetic patients worldwide. It has been suggested that urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were not the only indicators of renal function impairment in DKD and that they were also associated with diabetic peripheral neuropathy (DPN) which might affect nerve conduction velocity (NCV). As 30-40% of DPN patients had no subjective symptoms, while current perception threshold (CPT) could detect sensory nerve damage at an early stage. As a result, we aimed to investigate correlation between UACR, eGFR and CPT in DKD patients. METHODS: A total of 273 DKD patients from the First Affiliated Hospital of Kunming Medical University from January 2018 to June 2020 were enrolled to complete the CPT test. CPT values of the bilateral median nerve and superficial and deep peroneal nerves at 2000 Hz, 250 Hz, and 5 Hz were collected. RESULTS: In normoesthesia and hypaesthesia patients with DKD, MDRD-eGFR correlated negatively with TC (r = -0.135, P = 0.037), left superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.205, P = 0.001) and right superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.154, P = 0.017). Besides, left and right superficial peroneal and deep peroneal nerve 2000 Hz CPT correlated with CKD-EPI-eGFR and UACR. Multivariate logistic regression analysis found left superficial peroneal and deep peroneal nerve 2000 Hz CPT was independently associated with both MDRD-eGFR and CKD-EPI-eGFR. CONCLUSION: Decreased MDRD-eGFR and CKD-EPI-eGFR were expected to be a predictor of peripheral nerve injury in normoesthesia and hypaesthesia patients with DKD.

Mechanism of Erzhiwan on Hepatocellular Carcinoma Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To explore the possible mechanisms of Erzhiwan in the treatment of hepatocellular carcinoma (HCC) based on the network pharmacology. Method::The candidate active components and targets of Ligustri Lucidi Fructus and Ecliptae Herba were obtained through retrieval of the traditional Chinese medicine (TCM) systems pharmacology database (TCMSP) and literatures. Through Uniprot database and the human genome database (GeneCards), the overlapping genes of Erzhiwan and hepatocellular carcinoma were collected. The " candidate active components-targets" network of Ligustri Lucidi Fructus and Ecliptae Herba was built with Cytoscape 3.6.0 software. Drug target proteins and disease targets were mapped, and Venn map was drawn by Omicshare database. Major targets interaction network was formed by using String database and " Generate style from statistics" tool in Cytoscape 3.6.0 software. Molecular docking with active components was carried out by Systems Dock Web Site. The Gene Ontology (GO) classification enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the targets were carried out in DAVID database. Result::Totally 21 active components, including beta-sitosterol, quercetin, luteolin, demethylwedelolactone, kaempferol, and 151 targets, including tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), N-terminal kinase (JUN), proto-oncogene (c-MYC), matrix metalloproteinase-9 (MMP-9) of Erzhiwan were collected. Erzhiwan exerts its effects on HCC mainly by acting on signal pathways, including Hepatitis B, TNF, Phosphatidylinositol-3-kinase (PI3K/Akt), tumor suppressor gene p53 and Toll-like receptor. Conclusion::Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways of Erzhiwan in the treatment of HCC, providing a direction for further studies.

Serum endocan and circadian heart rate variability in non-dialysis stage 5 chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We investigated the link between serum endocan and circadian heart rate variability in non-dialysis stage 5 CKD patients. METHODS: In a cross-sectional study, we enrolled 54 prevalent n non-dialysis stage 5 CKD patients (32 males, aged 48.2 ± 14.92 years). HR was measured with an automatic system. Serum endocan level was analyzed by ELISA. RESULTS: Night/day HR ratio was independently predicted by serum endocan level (P < 0.01) and hypertension history (P < 0.05). Adjusted R2 of the model was 0.222. CONCLUSION: Increased serum endocan is significantly associated with circadian heart rate variability in non-dialysis stage 5 CKD patients. Further investigation is needed to explore the potential benefits of serum endocan lowering therapy in this patient group.

microRNA­145 modulates migration and invasion of bladder cancer cells by targeting N­cadherin.

MicroRNA (miRNA)­145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA­145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA­145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA­145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription­quantitative polymerase chain reaction. miRNA­145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA­145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N­cadherin was the direct target of miRNA­145. Subsequently, expression of N­cadherin and matrix metalloproteinase­9 (MMP9) in BC cells were detected by western blot analysis. miRNA­145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA­145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N­cadherin was identified as a target of miRNA­145 in BC cells. MMP9, acting downstream of N­cadherin, was downregulated in BC cells by miRNA­145. In the present study, miRNA­145 suppressed the migration and invasion of BC cells by regulating N­cadherin. The results of the present study indicated that miRNA­145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.

Sagittal abdominal diameter and Framingham risk score in non-dialysis chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that abdominal obesity is a risk factor for cardiovascular mortality. We investigated the link between sagittal abdominal diameter (SAD) and Framingham risk score in non-dialysis CKD patients. METHODS: In a cross-sectional study, we enrolled 307 prevalent non-dialysis CKD patients (175 males, aged 50.7 ± 17.04 years). SAD and Framingham risk score were measured. RESULTS: Framingham cardiovascular disease risk score was independently predicted by SAD (P < 0.01), GFR (P < 0.01) and diabetic history (P < 0.05). Adjusted R2 of the model was 0.178. SAD could be independently predicted by BMI (P < 0.01), diabetic history (P < 0.01), GFR (P < 0.01) and age (P < 0.01). Adjusted R2 of the model was 0.409. Using receiver operating characteristic (ROC) curve, a cutoff SAD value of 16.55 cm was determined with sensitivity of 63.7%, specificity of 58.3%. CONCLUSION: Elevated SAD is significantly associated with increased Framingham risk score in non-dialysis CKD patients. SAD can be predicted by patients' BMI, diabetic history, renal function and age. Further investigation is needed to explore the potential benefits of central obesity lowering therapy in this patient group.

miR-200b-containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial-mesenchymal transition.

BACKGROUND AND AIM: Epithelial-mesenchymal transition (EMT), characterized by the decrease of E-cadherin (E-Cad) and increase in vimentin and alpha-smooth muscle actin (α-SMA), was demonstrated to participate in inflammatory bowel disease-related fibrosis. miR-200b plays an anti-fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR-200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR-200b in the treatment of fibrosis. METHODS: Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR-200b. The MVs packaged with miRNA-200b were harvested for the anti-fibrotic treatment using in vitro (transforming growth factor beta 1-mediated EMT in intestinal epithelial cells: IEC-6) and in vivo (TNBS-induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E-Cad, vimentin, α-SMA, ZEB1, and ZEB2, were detected. RESULTS: MiR-200b-MVs would significantly reverse the morphology in TGF-ß1-treated IEC-6 cells and improve the TNBS-induced colon fibrosis histologically. The treatment of miR-200b-MVs increased miR-200b levels both in the IEC-6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E-Cad was increased, and the expressions of vimentin and α-SMA were decreased. ZBE1 and ZEB2, the targets of miR-200b, were also decreased. CONCLUSIONS: miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2.

Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis.

The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1ß (IL-1ß) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.

Differential Diagnosis of Benign and Malignant Breast Tumors Using Apparent Diffusion Coefficient Value Measured Through Diffusion-Weighted Magnetic Resonance Imaging.

OBJECTIVE: Apparent diffusion coefficient (ADC) value measurement of nodes in diffusion-weighted imaging was widely used in differentiating different types of human tumors. The aim of this meta-analysis was to evaluate the clinical value of ADC measurement through diffusion-weighted magnetic resonance imaging (DW-MRI) in the differential diagnosis of benign and malignant breast tumors. METHODS: Relevant studies were identified through computer-based search of databases, which were supplemented through manual search strategies. Case-control studies were selected in adherence with our strict inclusion and exclusion criteria. Statistical analysis was conducted using Stata 12.0 statistical software (StataCorp, College Station, Tex). RESULTS: Our database searches initially retrieved 602 studies (320 studies in Chinese and 282 studies in English), and 31 studies (18 studies in English and 13 studies in Chinese) were eventually selected for meta-analysis. These 31 case-control studies included a total of 926 normal breast tissues and 2323 breast tumors (911 benign tumors and 1412 malignant tumors). Our meta-analysis showed that ADC values measured through DW-MRI were higher in benign breast tumors compared with malignant breast tumors, and this difference was statistically significant. In addition, the ADC values in the normal breast tissues were markedly higher than the benign breast tumors, which were also at a statistically significant level. Consistent with these observations, the ADC values in the normal breast tissues were significantly higher when compared with the values found in the malignant breast tumors. CONCLUSIONS: Our data strongly support the conclusion that the ADC value measured through DW-MRI is an important radiographic index for differential diagnosis of benign and malignant breast tumors and is critical to our assessment of the internal structure of tumors.

Role of DOR-ß-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis.

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-ß-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, ß-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, ß-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-ß-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-ß-arrestin1-Bcl-2 signal transduction pathway.

Active components with inhibitory activities on IFN-γ/STAT1 and IL-6/STAT3 signaling pathways from Caulis Trachelospermi.

Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1) with IC50 value of 2.43 µg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3) with IC50 value of 1.38 µg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1) and nortrachelogenin 4-O-ß-D-glucopyranoside (2), together with six known compounds. The lignan compounds 1-4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 µM and 9.46 µM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 µM, 6.47 µM and 2.92 µM, respectively.

Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR-ß-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-ß-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway. MATERIALS AND METHODS: Eighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5 g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, ß-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined. RESULTS AND CONCLUSIONS: The expressions of DOR, ß-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, ß-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, ß-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-ß-arrestin1-Bcl-2 signal transduction pathway.

Role of DOR-β-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis / 华中科技大学学报（医学）（英德文版）

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.

Role of DOR-β-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis / 华中科技大学学报（医学）（英德文版）

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.

Increased dialysate levels of phospholipids containing unsaturated fatty acid are associated with increased peritoneal transport rate.

BACKGROUND: High peritoneal transport status in end-stage renal disease patients receiving peritoneal dialysis was shown to be associated with increased morbidity and mortality. Although the pathogenesis of increased peritoneal transport is still not clear, previous studies have demonstrated that phospholipids (PLs) are present on the peritoneal mesothelium and when added to dialysate can decrease the peritoneal fluid absorption rate and increase peritoneal fluid removal. In the present report, we explored the relationship between peritoneal transport and dialysate loss of endogenous PLs. METHODS: We evaluated 48 prevalent continuous ambulatory peritoneal dialysis patients with high or low peritoneal transport in a cross-sectional study. The 4-hour dwell dialysate PL profile was analyzed by high-performance liquid chromatography coupled with electrospray ionization ion trap mass spectrometry. The patients' peritoneal small solute transport rate was assessed by D/P(Cr) at 4 h and their fluid transport by kinetic modeling. RESULTS: While there were no significant differences between the 2 groups in age, sex, diabetic status and time on dialysis, high transporters had a significantly higher D/P(Cr) and peritoneal fluid absorption rate (K(e)) than low transporters. The PLs in dialysate effluents mainly consisted of PLs containing unsaturated fatty acid, and the concentrations, as well as the amount, of PLs were significantly elevated in the dialysate of high transporters as compared to low transporters. CONCLUSION: Our results showed that dialysate from high transporters exhibited elevated levels of PLs, especially PLs containing unsaturated fatty acid, suggesting a possible loss of peritoneal surface-active PLs in peritoneal dialysis, and this loss may contribute to the alteration in peritoneal transport.

Association between arterial stiffness and peritoneal small solute transport rate.

While cardiovascular disease accounts for 40-50% of the mortality in dialysis patients, and while a high peritoneal transport in continuous ambulatory peritoneal dialysis (CAPD) is an independent predictor of outcome, it is unclear if there are any links. Aortic stiffness has become established as a cardiovascular risk factor. We thus studied pulse wave velocity (PWV) in CAPD patients to explore the possible link between peritoneal small solute transport and aortic stiffness. CAPD patients (n = 76, 27 M/49 F) in our center were included in the present study. Aortic stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral PWV. Patients' peritoneal small solute transport rate was assessed by D/P(cr) at 4 h. Extracellular water over total body water (E/T ratio) was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Carotid-femoral PWV was positively associated with patients' age (r = 0.555; P < 0.01), time on peritoneal dialysis (r = 0.332; P < 0.01), diabetic status (r = 0.319; P < 0.01), D/P(cr) (r = 0.241; P < 0.05), PP (r = 0.475; P < 0.01), and E/T (r = 0.606; P < 0.01). In a multivariate regression analysis, carotid-femoral PWV was independently determined by E/T (P < 0.01), PP (P < 0.01), age (P < 0.01), and D/P(cr) (P < 0.05). D/P(cr), in addition to E/T, age, and PP, was an independent predictor of elevated carotid-femoral PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased peritoneal small solute transport rate.