Inhibition of ASM activity ameliorates DSS-induced colitis in mice.

Acid sphingomyelinase (ASM) is a membrane lipid hydrolase, acting to generate ceramide and regulate cell functions and inflammatory responses.The roles of ASM in mediating T cell functions are postulated whereas its function in regulation of macrophages remains uncertain. The study was performed to explore ASM activity in control of macrophage functions. RAW 264.7 cells were pretreated with desipramine, an ASM inhibitor, prior to LPS challenge in vitro. LPS initiated ASM activity in RAW 264.7 cells. Conversely, inhibition of ASM activity by desipramine diminished LPS induced ASM activities and TNF production of RAW 264.7 cells. The DSS colitis in mice was induced, and desipramine was administered to the mice two days post induction of colitis. Murine colitis was characterized by elevation of ASM activities in colon tissues. Desipramine administration overrode ASM activities in colon, and ameliorated DSS-induced colitis evidenced with the reduced disease activities and the decreased cytokine levels. Together, our data show a crucial role of ASM activity in regulation of macrophage functions and responses, and suggest that ASM represents a novel therapeutic approach for the management of immune diseases.

Inhibition of NADPH oxidase activities ameliorates DSS-induced colitis.

NADPH oxidases (NOX) act to generate reactive oxygen species (ROS) and exhibit microbicidal bioactivity, whereas their roles in mediating immune responses of inflammation in intestine remain to be further elucidated. The study was performed to explore the effects of NOX activity on regulation of macrophage functions. Macrophage responses were induced by lipopolysaccharides (LPS) in RAW 264.7 cells (in vitro) or dextran sulfate sodium (DSS) in BALB/c mice (in vivo) respectively. LPS induced NOX2 expression and initiated NOX activities in RAW 264.7 cells. Conversely, inhibition of NOX activity by DPI and VAS2870 diminished LPS induced NOX activities and the downstream signaling in RAW 264.7 cells. Murine colitis was characterized by macrophage accumulation and elevation of NOX activities in colon tissues. DPI and VAS2870 administration overrode NOX activities and ROS productions in colon tissues, and ameliorated DSS-induced colitis evidenced with the reduced disease activities and the decreased cytokine levels. Intriguingly, NOX2 expression levels were elevated in colon tissues of patients with active inflammatory bowel disease. Together, our data show a crucial role of NOX activity in regulation of macrophage functions and responses, and suggest that NOX represents a novel therapeutic approach for the management of immune diseases.

Outcomes of preoperative endoscopic nasobiliary drainage and endoscopic retrograde biliary drainage for malignant distal biliary obstruction prior to pancreaticoduodenectomy.

AIM: To compare the outcomes of preoperative endoscopic nasobiliary drainage (ENBD) and endoscopic retrograde biliary drainage (ERBD) in patients with malignant distal biliary obstruction prior to pancreaticoduodenectomy (PD). METHODS: Data from 153 consecutive patients who underwent preoperative endoscopic biliary drainage prior to PD between January 2009 and July 2016 were analyzed. We compared the clinical data, procedure-related complications of endoscopic biliary drainage (EBD) and postoperative complications of PD between the ENBD and ERBD groups. Univariate and multivariate analyses with odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to identify the risk factors for deep abdominal infection after PD. RESULTS: One hundred and two (66.7%) patients underwent ENBD, and 51 (33.3%) patients underwent ERBD. Endoscopic sphincterotomy was less frequently performed in the ENBD group than in the ERBD group (P = 0.039); the EBD duration in the ENBD group was shorter than that in the ERBD group (P = 0.036). After EBD, the levels of total bilirubin (TB) and alanine aminotransferase (ALT) were obviously decreased in both groups, and the decreases of TB and ALT in the ERBD group were greater than those in the ENBD group (P = 0.004 and P = 0.000, respectively). However, the rate of EBD procedure-related cholangitis was significantly higher in the ERBD group than in the ENBD group (P = 0.007). The postoperative complications of PD as graded by the Clavien-Dindo classification system were not significantly different between the two groups (P = 0.864). However, the incidence of deep abdominal infection after PD was significantly lower in the ENBD group than in the ERBD group (P = 0.019). Male gender (OR = 3.92; 95%CI: 1.63-9.47; P = 0.002), soft pancreas texture (OR = 3.60; 95%CI: 1.37-9.49; P = 0.009), length of biliary stricture (≥ 1.5 cm) (OR = 5.20; 95%CI: 2.23-12.16; P = 0.000) and ERBD method (OR = 4.08; 95%CI: 1.69-9.87; P = 0.002) were independent risk factors for deep abdominal infection after PD. CONCLUSION: ENBD is an optimal method for patients with malignant distal biliary obstruction prior to PD. ERBD is superior to ENBD in terms of patient tolerance and the effect of biliary drainage but is associated with an increased risk of EBD procedure-related cholangitis and deep abdominal infection after PD.

An alternative technique for Descemet's membrane detachment following phacoemulsification: case report and review of literature.

BACKGROUND: Descemet's membrane detachment (DMD) is one of the most serious complications of modern cataract surgery. We present an alternative technique for management of DMD with a review of the literature on current strategies for the treatment of DMD. CASE PRESENTATION: A 74-year-old woman developed DMD after phacoemulsification and failed the first descemetopexy with air tamponade. An alternative method was used to drain the pre-descematic fluid and reposition the detached Descemet's membrane in this rare case. This technique involved completely filling the anterior chamber with an intracameral air injection, followed by using a 23-gauge needle to puncture the peripheral cornea to drain the pre-descematic fluid. The Descemet's membrane was completely reattached to the stroma during the follow-up. CONCLUSIONS: Drainage of pre-descematic fluid combined with intracameral air tamponading was used as an alternative surgical option for the management of this severe case of DMD.

Metabolic syndrome risk factors and dry eye syndrome: a Meta-analysis.

AIM: To explore the relationship between metabolic risk factors and dry eye syndrome (DES). METHODS: Retrieved studies on the association of metabolic syndrome risk factors (hypertension, hyperglycemia, obesity, and hyperlipidemia) and DES were collected from PubMed, Web of Science, and the Cochrane Library in December 2015. Odds ratio (OR) with 95% confidence interval (CI) were pooled to evaluate the final relationship. Subgroup analyses were conducted according to diagnostic criteria of DES. RESULTS: Nine cross-sectional studies and three case-control studies were included in this Meta-analysis. The pooled results showed that people with hypertension, hyperglycemia, and hyperlipidemia had a higher risk of suffering from DES (P<0.05), especially the typical DES symptoms. On the other hand, obesity did not increase the risk of DES. CONCLUSION: The present Meta-analysis suggests that all metabolic risk factors except obesity were risk factors for DES.

Two modified surgical procedures for treating early stage breast cancer in China.

Conventional pedicled-flap based surgeries in treating breast cancer have their limitations. New surgical regimens are yet to be explored, which will follow the oncological principle of being "total tumor free", whilst fit into the unique characteristics of China's own medical system as well as patients' demand. From 2007 to 2013, 143 patients with early stage breast cancer were included in the study, with the average age of 46.1 years. Fifty-three patients were subjected to modified breast conserving surgery (MBCS)+latissimus dorsi (LD) flap reconstruction, 41 to skin sparing mastectomy (SSM)+implant+LD flap reconstruction, 29 to MBCS+distal transverse rectus abdominis myocutaneous (DTRAM) flap reconstruction, and 20 to SSM+DTRAM flap reconstruction. The results showed that out of the 143 patients, there was no graft loss. Minor complications included 4 cases of fat liquefaction, and 6 cases of seratoma, which all resolved after conservative treatment. Five patients had visible protuberance in the abdomen, but not leading to any gastrointestinal symptoms. The reconstructed breasts all presented good shape. 96.7% of the patients were satisfied with the outcome. The follow-up period varied from 6 months to 60 months, and only one patient died from tumor metastasis in the brain. No local recurrence occurred. It was concluded that these two modified pedicled-flap surgeries are readily practical, and aesthetically satisfactory, with high applicability in China. They do not compromise the oncological outcomes, but also are well-accepted by Chinese patients.

[Analysis of apoptosis-related gene expression in different serum level of insulin-like growth factor-1 in mice breast cancer tissue].

OBJECTIVE: A stable primary breast cancer model in liver-specific insulin-like growth factor 1 (IGF-1) deficient (LID) mice and control mice was established. To screen apoptosis related genes expression in different serum IGF-1 levels by gene chip and flow cytometry. METHODS: The LID mice and control mice were used. Induction of breast cancer was achieved by using the 7,12-dimethylbenz(a) anthracene. Ginsenoside Rg3 was used to interfering therapy treatment. The incidence of breast cancer in every group was compared, and expression of apoptosis associated genes was detected by gene chip and flow cytometry. RESULTS: The incidence of tumor in none ginsenoside Rg3 injected control mice was 66.7%. The incidence of tumor in ginsenoside Rg3 injected LID mice was 12.0% which was significantly lower than any other group (P < 0.05). The apoptosis percentage in none ginsenoside Rg3 injected control mice was (2.7 +/- 0.7)%. The apoptosis percentage in ginsenoside Rg3 injected LID mice was (14.0 +/- 1.7)%. The results of gene chip indicated that in contrast to LID mice, LTA, LTB, TNF-alpha, TRAIL, TRANCE, BLK, BOK, CASP8, TRAF5, and APAF1 genes were down-regulated, and LTBR, TRAF4 genes were up-regulated in the breast cancer tissues of control mice. Application of ginsenoside Rg3 therapy could change the expression of these genes. CONCLUSIONS: Circulating IGF-1 levels play a role in the onset and development of breast cancer. Degrade serum IGF-1 level is able to promote apoptosis by affecting the expression of a series of apoptosis related genes consequently inhibit the growth of breast cancer. There was a synergistic effect with the application of ginsenoside Rg3.

[Different expression of liver-specific insulin-like growth factor I gene in breast cancer; expression with mice].

OBJECTIVE: To investigate the possible relationship between liver-specific insulin-like growth factor I (IGF-1) and the pathogenesis of breast cancer. METHODS: Fifty non-IGF-1 deficient (LID) mice were randomly divided into 2 equal groups: Group I, fed with dimethyl-benzanthracene (DMBA) for 8 weeks to cause mammary cancer, and Group III, fed with DMBA and ginsenoside Rg for 28 d; and 50 LID mice were randomly divided into 2 equal groups too Group II, fed with DMBA for 8 weeks, and Group IV, fed with DMBA and ginsenoside Rg for 28 d. The mice were killed after the cessation of DMBA use. The serum IGF-1 expression was detected with method Six Gene chips were used to detect the gene expression in the breast cancer tissues. RESULTS: The breast cancer rates were 66.67% in Group I and 33.33% in Group II, 36.00% in Group III, and 12.00% in Group IV. The tumor size was (0.79 +/- 0.20) cm in Group I, (0.37 +/- 0.08) cm in Group III , (0.32 +/- 0.08) cm in Group II, and (0.15 +/- 0.05) cm Group IV. The IGF-1 level of Group II was (41.33 +/- 7.52) ng/ml, 1/4 as high as that of Group I [(166.51 +/- 12.32) ng/ml], and the IGF-1 level of Group IV was (33.48 +/- 6.73) ng/ml, 1/4 as high as that of Group III [(155.84 +/- 11.34) ng/ml]. Compared with those of the control mice, the breast cancers of the LID mice had longer latency, lower incidence, and slower growth rate. The differential gene expression in different serum IGF-1 levels involved binding, metabolism, apoptosis, cell cycle, signal transduction, immune response, transcription regulation and interpretation regulation and so on. Among these genes, Col11, Egln3, Glycam1, Irf6, Lgals7, Perp, Rag1, and Rbm35a genes were closely related to the incidence of breast cancer. CONCLUSION: IGF-1 plays a role as a risk factor in the onset and development of breast cancer by affecting the expression of many differentially expressed genes.

[Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice].

BACKGROUND & OBJECTIVE: Insulin-like growth factors (IGFs) play important roles in the development and progression of tumors. But the mechanism of tumorigenesis in relation to IGF-1 is unclear yet. This study was to explore the correlation of circulating IGF-1 level to the angiogenesis of breast cancer in IGF-1-deficient mice. METHODS: The liver-specific IGF-1-deficient (LID) mice and control mice were injected with 7,12-dimethybenz(a)anthracene (DMBA) to develop breast cancer. Ginsenoside Rg3 was used to intervene tumor growth. The occurrence rates of breast cancer were compared. The expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) was detected by immunohistochemistry. RESULTS: The occurrence rate of breast cancer was 66.67% in untreated control mice, 33.33% in untreated LID mice, 36.00% in Rg3-treated control mice, and 12.00% in Rg3-treated LID mice. The tumor size was (0.79+/-0.20) cm in untreated control mice, (0.37+/-0.08) cm in untreated LID mice, (0.32+/-0.08) cm in Rg3-treated control mice, and (0.15+/-0.05) cm in Rg3-treated LID mice. The average light density and positive rate of VEGF were the highest in untreated control mice (0.34+/-0.10 and 0.04+/-0.02, P<0.05), and the lowest in Rg3-treated LID mice (0.13+/-0.03 and 0.01+/-0.00, P<0.05). The MVD was 31.9+/-5.3 in untreated control mice, 26.8+/-4.9 in untreated LID mice, 20.1+/-4.9 in Rg3-treated control mice, and 14.4+/-4.9 in Rg3-treated LID mice. CONCLUSIONS: Circulating IGF-1 plays a role in the onset and development of breast cancer. Degrading serum IGF-1 level could inhibit angiogenesis and growth of breast cancer. Rg3 could promote this effect.