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Inflammatory Bowel Diseases (IBDs) are chronic disorders with iterative intestinal mucosal inflammation which remain unmet medical needs. PDE4 inhibitors were reported to be novel anti-IBD agents, but their clinical use was hampered by side effects such as emesis and nausea. Herein, structure-based discovery of natural mangostanin (1) targeting the M-pocket resulted in the novel and potent PDE4 inhibitor 22d (IC

To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P

Background: The liver cyst is a common disease in hepatobiliary surgery. Most patients have no apparent symptoms and are usually diagnosed accidentally during imaging examinations. The vast majority of patients with liver cysts follow a benign course, with very few serious complications and rare reports of malignant changes. Case Presentation: We present two cases of liver cysts that evolved into intrahepatic tumors during the follow-up process. The first patient had undergone a fenestration and drainage operation for the liver cyst, and the cancer was found at the cyst’s position in the third year after the procedure. Microscopically, bile duct cells formed the cyst wall. Tumor cells can be seen on the cyst wall and its surroundings to form adenoid structures of different sizes, shapes, and irregular arrangements, some of which are arranged in clusters. The second patient was regularly rechecked after discovering liver cysts, and a new mass appeared very close to the cyst. The clinical manifestations and laboratory examinations of the two patients lacked specificity, the preoperative diagnosis was unclear, and the postoperative pathology confirmed cholangiocarcinoma.Conclusions: Our cases indicate that liver cysts may lead to the occurrence of malignant intrahepatic cholangiocarcinoma. Therefore, follow-up of particular liver cysts is necessary, and the differential diagnosis of the intrahepatic cystic tumors needs to include cholangiocarcinoma.

Ginsenoside Rh2 is a potential active metabolite of ginseng that has antitumor activity against a variety of tumor cells. Previously, we reported that Rh2-O, an octyl ester derivative of ginsenoside Rh2, had a higher anti-cancer activity than Rh2 through activating the intrinsic apoptotic pathway. In this study, we found that the extrinsic apoptotic pathway was also involved in Rh2-O-induced HepG2 cells apoptosis as evidenced by the up-regulation of Fas, FasL, TNFR1 and TNF-α, as well as the cleavage of caspase 8. Moreover, flow cytometric analysis demonstrated that Rh2-O induced G1 cell cycle arrest in HepG2 cells. Rh2-O-induced G1 phase arrest was accompanied by the down-regulation of cyclin D3 and cyclin E and cyclin-dependent kinase (CDK) 4 and 6, and the up-regulation of p21WAF1/CIP1 and p27KIP1. In addition, Rh2-O down-regulated the phosphorylation of Akt, and its inhibitor LY294002 promoted Rh2-O-induced G1 phase arrest. Rh2-O treatment also activated p38 MAPK, JNK and ERK expression. Inhibitors of...

Endothelial inflammation is recognized as the initial stage of a multistep process leading to coronary heart disease (CHD). Recently, the different effects of industrial trans fatty acids (elaidic acid, 9t18:1) and ruminant trans fatty acids (vaccenic acid, 11t18:1) on CHD have been reported in epidemiological and animal studies, however, the mechanism was not fully studied. Therefore, the objective of this study was to explore the underlying mechanism by which 9t18:1 and 11t18:1 affect human umbilical vein endothelial cells (HUVECs) inflammation. We found that 9c11t-CLA modulated the inflammation of HUVECs induced by 9t18:1 and 11t18:1. Fatty acid composition, pro-inflammatory factors, phosphorylation of MAPKs, and the TLR4 level in HUVECs altered by 11t18:1 induction, collectively suggest that the bio-conversion of 11t18:1 to 9c11tCLA might be the cause why 11t18:1 and 9t18:1 have distinct influences on endothelial injuries. It was concluded that it is biosynthesis of 9c11t CLA from11t18:1, and the modulation of TLR4-MAPK pathway by 9c11t CLA, which at least partially account for the slight effect of 11t18:1 on endothelial inflammation.

To compare clinical outcome and quality of life of subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis (TAC-IRA) in patients with severe slow transit constipation (STC).Of the 56 patients enrolled in this study from January 1999 to June 2008, 32 cases underwent subtotal colectomy with antiperistaltic cecoproctostomy, and 20 patients underwent TAC-IRA. The patients' clinical characteristics, operative data, postoperative outcome, functional result and gastrointestinal quality of life index (GIQLI) survey were compared between the two groups.All patients were followed up for 1-7 years (median, 4 years). The basic clinical characteristics between the two groups was comparable. During the follow-up period, the number of daily bowel movements in the subtotal colectomy group was significantly fewer than that in TAC-IRA group (2.5+/-0.8 vs. 3.4+/-0.8; P=0.000). The Wexner continence score was significantly lower in subtotal colectomy group (4.4+/-1.6 vs. 5.8+/-1.9; P=0.011), and the GIQLI score in subtotal colectomy group was significantly higher than that in the TAC-IRA group (120.7+/-7.5 vs. 111.1+/-12.0; P=0.005).Subtotal colectomy with antiperistaltic cecoproctostomy appeared to be the superior treatment than the TAC-IRA for selected patients with slow transit constipation for improved functional outcomes and quality of life.

To compare the efficacy between subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis (TAC-IRA) for patients with severe refractory slow transit constipation(STC).During 1999 to 2002, TAC-IRA was the preferred procedure for 20 STC patients in our department. From 2003 to 2005, 17 STC patients underwent subtotal colectomy plus antiperistaltic cecoproctostomy. Clinical data of the two groups were collected and compared retrospectively.There were no significant differences in basic preoperative clinical data between the two groups. During the follow-up period, the time of daily defecation in the antiperistaltic cecoproctostomy group was less than that of TAC-IRA group (2.4+/-0.9 vs 3.4+/-0.8, P=0.0014), meanwhile the Wexner continence score was significantly lower in the antiperistaltic cecoproctostomy group (4.3+/-1.8 vs 5.8+/-1.9, P=0.0223). Barium enema after subtotal colectomy showed that residual ascending colon and cecum presented a sign of "reservoir".Subtotal colectomy with antiperistaltic cecoproctostomy is a better method for appropriately selected patients with STC than TAC-IRA.

To assess the long-term results after subtotal colectomy with antiperistaltic cecoproctostomy in idiopathic chronic slow-transit constipation.Between January 2003 and February 2004, 14 patients with chronic slow-transit constipation and 2 patients with mixed constipation underwent subtotal colectomy with antiperistaltic cecoproctostomy. The following information was collected during follow-up (mean 3 years): number of bowel movement, stool consistency, complications, quality of life and degree of satisfaction.There was no mortality or major postoperative complications. One month after the operation, bowel frequency was a mean of 4 daily, with a semi-liquid stool consistency. After 3 years, bowel frequency was a mean of 2 daily, with a semi-solid stool consistency. Although no patient used antidiarrheal medicine, laxatives continued to be used by one case with mixed chronic constipation. All patients reported a good or improved quality of life and satisfied with the results. Two patients developed adhesive ileus post operation. There was no diarrhea or incontinence occurred during the follow-up.Subtotal colectomy with end-to-end antiperistaltic cecoproctostomy for appropriately selected patients with slow-transit constipation results in consistent relief of constipation and satisfactory outcome.

AIM: To investigate the damaging effect of high-intensity focused ultrasound (HIFU) on cancer cells and the inhibitory effect on tumor growth. METHODS: Murine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length of time in vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically. RESULTS: The death rate of cancer cells treated with HIFU at 1 000 W/cm2 for 0.5, 1, 2, 4, 8, and 12s was 3.11±1.21%, 13.37±2.56%, 38.84±3.68%, 47.22±5.76%, 87.55±7.32%, and 94.33±8.11%, respectively. A positive relationship between the death rates of cancer cells and the length of HIFU treatment time was found (r = 0.96, P

Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1alpha and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1alpha and VEGF play important roles in tumor angiogenesis.HIF-1alpha mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1alpha and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1alpha protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD34 immunostaining in colorectal carcinomas.Optical density values representing HIF-1alpha mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P0.05) or in hypoxic conditions but treated with genistein (P0.05). The levels of HIF-1alpha and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P0.01, P0.05, respectively) and hypoxia/genistein group (P0.01, P0.05, respectively). The positive expression rates of HIF-1alpha mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes' stages (P0.05). HIF-1alpha mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P0.01). HIF-1alpha protein expression correlated significantly with VEGF protein expression and MVD.Hypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinomas. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.

Hypoxia-inducible factor-1 alpha (HIF-1alpha), a transcriptional factor response to hypoxia plays an important role in tumor angiogenesis. This study was designed to examine the expression of HIF-1alpha gene and its relationship with vascular endothelial growth factor (VEGF) protein and microvessel density (MVD).HIF-1alpha gene expression was analyzed using in situ hybridization, and VEGF expression levels were determined by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinomas. Microvessel density (MVD) was determined by anti-CD34 immunostaining.Positive expression of HIF-1alpha mRNA were found in 67.8% (42/62) of the colorectal adenocarcinomas and 44.4% (8/18) of the adenomas. The mean percentage of HIF-1alpha mRNA positive cells increased gradually with the development from Dukes'stage A to stage C+D (P0.05). The frequencies of HIF-1alpha positive cells in pathologic stage of the specimens were as follows: adenoma 8%, Dukes A 14%, Dukes B 23%, Dukes C+D 35%. The positive expression rate of VEGF protein in colorectal adenocarcinoma group was significantly higher than that in colorectal adenoma group (59.7% vs 33.3%,P0.05). During colorectal tumor progression, the expression of HIF-1alphamRNA was positively correlated with the VEGF protein expression and MVD (r(s) = 0.768 P0.01 and r(s) = 0.683 P0.05, respectively).These results suggest that tumor angiogenesis induced by HIF-1alpha mRNA and VEGF protein might play an important role in tumorigenesis of colorectal adenoma and progression of colorectal cancer.

AIM: To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP). METHODS: Seventy patients with SAP admitted from Jan. 1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were compared. RESULTS: The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16% vs 30%, P < 0.05 and 9% vs 30%, P < 0.01, respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole group. CONCLUSION: Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with SAP. But once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective.