In vivo and in vitro anti-sepsis effects of physcion 8-O-β-glucopyranoside extracted from Rumex japonicus / 中国天然药物

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-β-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg, i.p.) on sepsis. Cytokines including TNF-α, IL-1β and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 μg·mL) significantly decreased the TNF-α, IL-1β and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 μg·mL (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.

Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the effect of atorvastatin on lipopolysaccharide (LPS)-induced TNF-α production in RAW264.7 macrophages.</p><p><b>METHODS</b>RAW264.7 macrophages were treated in different LPS concentrations or at different time points with or without atorvastatin. TNF-α level in supernatant was measured. Expressions of TNF-α mRNA and protein and heme oxygenase-1 (HO-1) were detected by ELISA, PCR, and Western blot, respectively. HO activity was assayed.</p><p><b>RESULTS</b>LPS significantly increased the TNF-α expression and secretion in a dose- and time-dependent manner. The HO-1 activity and HO-1 expression level were significantly higher after atorvastatin treatment than before atorvastatin treatment and attenuated by SB203580 and PD98059 but not by SP600125, suggesting that the ERK and p38 mitogen-activated protein kinase (MAPK) pathways participate in regulating the above-mentioned effects of atorvastatin. Moreover, the HO-1 activity suppressed by SnPP or the HO-1 expression inhibited by siRNA significantly attenuated the effect of atorvastatin on TNF-α expression and production in LPS-stimulated macrophages.</p><p><b>CONCLUSION</b>Atorvastatin can attenuate LPS-induced TNF-α expression and production by activating HO-1 via the ERK and p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of inflammatory diseases such as sepsis, especially in those with atherosclerotic diseases.</p>

Effect of protease in the lumen of rat intestine on inflammatory reaction during hemorrhagic shock / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of intraluminal administration of ulinastatin (a protease inhibitor) in the intestine on intestinal inflammation in rats with hemorrhagic shock.</p><p><b>METHODS</b>Twenty-eight Wistar rats were randomized into control group (A), intestinal saline perfusion group (B), ulinastatin intestinal perfusion group (C), and intravenous ulinastatin injection group (D) (n=7). The mean arterial blood pressure (MAP) and survival time of the rats were recorded. The changes in human polymorphonuclear cell (PMN) CD11b expression were detected by flow cytometry. The leukocyte count was recorded at different time points after the treatment, and the pathology of the intestinal mucosa was observed comparatively.</p><p><b>RESULTS</b>Groups C and D showed significantly slower reduction of the MAP than groups A and B after hemorrhagic shock (P<0.05). The survival time of the rats was the longest in group C (P<0.05). CD11b expression increased gradually during hemorrhagic shock in all the groups, but the expression level was the lowest in group C (P<0.05). Hemorrhagic shock caused a reduction in leukocyte counts, which remained the highest in group C (P<0.05). Group C also showed the least intestinal pathology among the 4 groups.</p><p><b>CONCLUSION</b>Intestinal perfusion of ulinastatin can lower the reduction rate of MAP, attenuate plasma activation and intestinal inflammation, and prolong the survival of rats with hemorrhagic shock. These results indicate an important role of protease in intestinal inflammation during hemorrhagic shock.</p>

Pharmacokinetics and pharmacodynamics of poly (lactide-co-glycolide) microspheres containing ropivacaine and dexamethasone for sciatic nerve block in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the pharmacokinetics and pharmacodynamics of poly (lactide-co-glycolide) microspheres containing ropivacaine and dexamethasone for sciatic nerve block in mice.</p><p><b>METHODS</b>A total of 165 female mice were randomly assigned into 3 groups, namely dexamethasone-loaded ropivacaine microsphere group (group A, n=55), ropivacaine microsphere group (group B, n=55) and PLGA microsphere group (group C, n=55). The mice received surgical implantation of the corresponding preparations near the sciatic nerve at the dose of 400 mg/kg. Hot plate test was used to evaluate the anesthetic effect of these microspheres at different time points after the implantation, and high-performance liquid chromatography (HPLC) was employed to determine plasma ropivacaine concentration.</p><p><b>RESULTS</b>Pharmacodynamic study showed that the duration of sciatic nerve sensory block was significantly longer in group A than in group B (P<0.05). The analysis of pharmacokinetics variables demonstrated that T(1/2) in group A was prolonged as compared with that of group B. No anesthetic effect was observed in group C.</p><p><b>CONCLUSION</b>Dexamethasone-loaded ropivacaine microspheres can significantly prolong the analgesic effect of ropivacaine in mice.</p>

Relationship between breast cancer molecular subtypes with clinicopathological characteristics and prognosis / 中华病理学杂志

<p><b>OBJECTIVES</b>This study try to subclassify breast cancer into different prognostic subgroups according to immunohistochemical algorithm and discuss the relationship between subtypes and biological and clinical behavior and prognosis.</p><p><b>METHODS</b>One hundred and twenty-eight cases of infiltrative ductal carcinoma were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2 and CK5/6 and subclassified referring to previous reports, and the 9 cases of HER2 positive subtype were tested using FISH.</p><p><b>RESULTS</b>The expression of ER, PR, HER2, and CK5/6 was detected in 67%, 45%, 27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A (55%), luminal B (20%), HER2 positive (7%), basal-like (10%) and unclassified cases (8%). Nine HER2 positive cases all showed amplification of HER2 gene. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes.</p><p><b>CONCLUSION</b>According to the expression of ER, PR, HER2 and CK5/6, infiltrative ductal carcinoma could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment.</p>

Early goal-directed therapy lowers the incidence, severity and mortality of multiple organ dysfunction syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of early goal-directed therapy (EGDT) on the incidence, severity and mortality of multiple organ dysfunction syndrome (MODS).</p><p><b>METHODS</b>A prospective, randomized controlled trial was performed involving 273 patients in the early stage of shock at risk of potential MODS development. The patients were randomly divided into EGDT group (including 139 patients managed with EGDT) and control group (including 134 patients with conventional empirical therapy). The scores of APACHE II, blood lactate concentration (Lactate(0)) and SOFA scores (SOFA(0)) of the two groups were recorded on admission, and the lactate concentration on the second and fourth day of hospitalization (Lactate(2) and Lactate(4)), and the highest SOFA scores (SOFAT) after admission were also recorded. The discrepancy between the two SOFA scores (SOFA(S)), number of the dysfunctional organ, and the mortality in ICU of the two groups were calculated at the end of the study.</p><p><b>RESULTS</b>The incidence of MODS in the EGDT group was significantly lower than that in control group (P=0.002). The Lactate(2), Lactate(4), SOFA(T), SOFA(S), and the number of dysfunctional organs in EGDT group were also significantly lower (P=0.045, 0.016, 0.009, 0.010, 0.002). EGDT was associated with a significantly lower total mortality rate of MODS than the conventional therapy (P=0.007), and also with a significantly lower mortality rate of MODS after controlling for severe sepsis (P=0.047 and 0.044).</p><p><b>CONCLUSION</b>EGDT can decrease the incidence and severity of MODS, and can effectively decrease the mortality of MODS irrespective of the presence of severe sepsis.</p>

Effects of subanesthetic dose of ketamine on perioperative serum cytokines in orthotopic liver transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effects of ketamine on perioperative serum cytokine levels in patients undergoing orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>Twenty patients undergoing OLT were randomly divided into ketamine group (n=10) and control group (n=10). Patients in ketamine group were given intravenous bolus injection of ketamine at 0.25 mg/kg followed by ketamine infusion at 0.5 mg.kg(-1).h(-1) until the end of operation except in the anhepatic phase, whereas the control group received saline of the same amount. Arterial blood samples were obtained at the start of surgery (T(1)), 5 min before the anhepatic phase (T(2)), 5 min before recirculation (T(3)), 15 and 60 min after recirculation (T(4), T(5)), and 0, 4 and 24 h after operation (T(6), T(7), T(8)). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 were measured by ELISA.</p><p><b>RESULTS</b>Serum TNF-alpha, IL-6 and IL-10 levels increased significantly during anhepatic phase as compared with the baseline level (T(1)) (P<0.05), and the changes were especially obvious in IL-6 and IL-10. The levels of the cytokines kept rising after recirculation and reached the peak level at T(5)(P<0.05), followed then by rapid decline and still maintaining higher levels than the preoperative ones 24 h after operation. The levels of TNF-alpha in ketamine group between T(2) and T(7) were significantly lower than that in the control group, and the IL-6 level between T(2) and T(5) were also significantly lower in ketamine group. Serum IL-10 level did not show any significant difference between the two groups.</p><p><b>CONCLUSION</b>Ischemia and reperfusion injury of the liver and surgical stress induce pro- and anti-inflammatory cytokine responses during liver transplantation, in which event IL-6 and IL-10 are more sensitive than TNF-alpha. Ketamine can inhibit the production of TNF-alpha and IL-6 but not IL-10.</p>

Prevention and management of lung infections with thymosin alpha1 in critical patients with tracheotomy / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the preventive and therapeutic effect of thymosin alpha(1) on lung infections in critical patients with tracheotomy.</p><p><b>METHODS</b>Forty-two patients were randomly divided into treatment group and control group to receive daily subcutaneous thymosin injection at 11.6 mg and saline of 2 ml for 7 days, respectively.</p><p><b>RESULTS</b>Compared with the control group, the infection rate, white blood cell count, C-reactive protein, tumor necrosis factor-alpha and interleukiu-6 were significantly lower in the treatment group.</p><p><b>CONCLUSION</b>Thymosin alpha(1) can be effective for prevention and treatment of lung infections in critical patients with tracheotomy and may improve the patients' immunity and prognosis.</p>

Correlation study of expression levels of prostate-specific membrane antigen and prostate-specific antigen with Gleason score of prostate carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the correlation of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) expression with Gleason score of prostate carcinoma.</p><p><b>METHODS</b>Monoclonal antibodies against epitopes of PSMA extracellular domain were prepared, with which the expression of PSMA of prostate carcinoma (PC) was determined by immunohistochemical staining. Correlation of its expression with Gleason score of PC was statistically analyzed, and compared with that of PSA.</p><p><b>RESULTS</b>Eight hybridoma cell lines secreting monoclonal antibodies specific for PSMA were prepared. PSMA expression level was positively correlated with Gleason score. In poorly differentiated prostate carcinoma, the expression intensity of PSMA was higher than that of medium-and well-differentiated prostate carcinoma (P < 0.01). However, there was no correlation between level of PSA expression and Gleason score (P > 0.05).</p><p><b>CONCLUSION</b>PSMA expression level may be used as a useful surrogate marker in Gleason grading of prostate carcinoma. It may be a more suitable target than PSA in antibody mediated immunotherapy against poorly differentiated prostate carcinoma which is usually not sensitive to hormonal therapy.</p>