BACKGROUNDUrinary trypsin inhibitor inhibits the enhanced production of pro-inflammatory molecules. Hemeoxygenase-1 induction protects against ischemia/reperfusion injury, oxidative stress, inflammation, transplant rejection, apoptosis, and other conditions. However, it is unknown if a combined hemin and ulinastatin pretreatment could result in protective effects for septic shock. In this study, we investigated the role of hemin pretreatment combined with ulinastatin on septic shock in rats.

METHODSEighty healthy, male Sprague-Dawley rats were randomly divided into four groups: group S, group H, group U and group HU. Groups S and U received 1 ml normal saline intraperitoneally, while groups H and HU both received 1 ml (100 mg /kg) hemin. Twenty-four hours later, 0.5 ml (10 mg/kg) E. coli lipopolysaccharide was injected intravenously to replicate the experimental model of septic shock. After an initial 25% decrease in the mean arterial pressure, corresponding to time point 0, groups HU and U received 0.5 ml 10 000 U/kg ulinastatin intravenously, and the others received 0.5 ml normal saline.

RESULTSThe number of deaths in groups H and U was lower than that in the group S (P < 0.05), and was higher than that in group HU (all P < 0.05) respectively. The mean arterial pressure (MAP) in the group S was significantly greater than that in group H (P < 0.05), and was lower than that in group HU and group U (P < 0.05). The plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and blood urea nitrogen (BUN), the malondial-dehyde (MDA) of liver, kidney and lung, and the lung Evans blue (EB) contents in groups H and U, were greater than that in group HU (all P < 0.05), and were lower than that in group S (all P < 0.05). In contrast, the plasma levels of CO in groups H and HU were higher than that in groups S and U (all P < 0.05), and SOD of liver, kidney and lung in groups H and U were higher than that in group S, and were lower than that in group HU (all P < 0.05). The levels of TNF-alpha, IL-6, IL-8 and beta-glucuronidase (GCD) activity of plasma in groups U and HU were lower than those in groups H and S, all having a P < 0.05, while there were no significant differences between group H and group S, or between group HU and group U (all P > 0.05). The HO-1 mRNA and HO-1 protein levels from hepatic, renal, and pulmonary tissue in groups S and U were lower than those in groups H and HU (all P < 0.05), but there were no significant differences between groups S and U, or between groups H and HU (all P > 0.05). The HO-2 mRNA and HO-2 protein were not significantly different among the four groups (all P > 0.05).

CONCLUSIONSCombined pretreatment with hemin and ulinastatin in septic shock rats results in an improved response by the upregulation of HO-1 protein followed by increasing CO with resistance to increased oxidative stress, restraining the release of inflammatory mediators, and inhibiting beta-GCD activity.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Pressure ; drug effects ; Blood Urea Nitrogen ; Creatinine ; blood ; Cytokines ; blood ; Glycoproteins ; therapeutic use ; Heme Oxygenase (Decyclizing) ; analysis ; genetics ; Hemin ; therapeutic use ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; drug therapy ; physiopathology ; Superoxide Dismutase ; metabolism

Objective To explore post-effect of acupuncturing ST36 (Zusanli) on brain functional connectivity. Methods Twelve healthy volunteers participated in this experiment. The fMRI data taken before and 25 minutes after removed acupuncturing stimulation were analyzed, while posterior cingulated cortex were chosen as seed points. Results At 25 minutes after removed acupuncturing stimulation, new increased functional connectivity were found in the left paracentral lobule, right superior parietal lobule and right postcentral gyrus. After acupuncture, there was intensity functional connectivity greater than in primary brain regions. Conclusion Post-effect of acupuncture can increase functional connectivity in healthy volunteer's brain.

OBJECTIVETo evaluate the efficacy and safety of posterior mediastinal route (PR) as compared with anterior mediastinal route (AR) after esophagectomy.

METHODSA systematic literature retrieval was carried out to obtain studies of randomized controlled trials (RCT) comparing PR with AR after esophagectomy before June 2012. Study selection, data collections and methodological quality assessments of retrieved studies were independently performed by two individual reviewers and meta-analysis was conducted using the RevMan 5.0 software.

RESULTSSix RCTs involving 376 patients (PR:197 cases, AR:179 cases) met the selection criteria. Meta-analysis showed that operative mortality (RR=0.49, 95%CI:0.18-1.36), anastomotic leaks (RR=0.95, 95%CI:0.44-2.07), cardiac morbidity (RR=0.51, 95%CI:0.25-1.04), pulmonary morbidity (RR=0.69, 95%CI:0.41-1.15), anastomotic strictures (RR=0.88, 95%CI:0.62-1.25), dysphagia (RR=1.26, 95%CI:0.75-2.11), 6-month body weight after esophagectomy were not significantly different between these two routes of reconstruction (all P>0.05).

CONCLUSIONAR should be the choice of reconstruction in view of its potential advantages in the prevention of tumor recurrence within the gastric conduit and avoidance of conduit irradiation when undergoing postoperative radiotherapy. However, further studies are needed to confirm the difference of long-term efficacy between the two routes.

Esophageal Neoplasms ; surgery ; Esophagectomy ; Gastroenterostomy ; methods ; Humans ; Randomized Controlled Trials as Topic ; Stomach ; surgery

This study was undertaken to analyze and evaluate the diagnosis and principal treatment methods for congenital choledochal cyst, focusing on various surgical procedures and clinical outcome. A comprehensive, retrospective study was conducted on 72 adult patients who presented with choledochal cyst from 1985 to 2002. Surgical procedures were cyst excision with hepaticojejunostomy in 25 cases for type I or type IV-B, extrahepatic cyst excision with hepaticojejunostomy in 8 cases for type IV-A, extrahepatic cyst excision with modified hepaticojejunostomy in 2 cases for type IV-B, non-cyst excision with or without hepaticojejunostomy in 27 cases for types I, II, IV-A, IV-B. The early postoperative morbidity and mortality rate were 16.1% (9/62) and 6.5% (4/62) respectively, and the complication rate related to surgical procedure was 30.6% (19/62). The incidence of cholangiocarcinoma with non-cyst excision or non-operated congenital choledochal cyst was 10.8% (4/37). One patient died of primary hepatocellular carcinoma after cyst excision with hepatojejunostomy. In conclusion, our results showed that complete exci-sion of choledochal cyst for types I, II, and IV-B and complete excision of extra-hepatic choledochal cyst from the hepatic hilum in type IV-A with hepaticojejunostomy or modified hepaticojejunostomy are the treatment of choice for choledochal cyst in adult patients.
Academic Medical Centers/trends ; Adolescent ; Adult ; Choledochal Cyst/*epidemiology/*surgery ; Female ; Hepatectomy/*methods/*statistics & numerical data ; Humans ; Jejunostomy/*methods/*statistics & numerical data ; Korea/epidemiology ; Male ; Middle Aged ; Postoperative Complications/*epidemiology ; Retrospective Studies ; Treatment Outcome

Because c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 33 inhibited both enzymes with the IC50 values of 0.0484 micromol x L(-1) and 34.5 micromol x (-1), respectively. Some of the compounds also showed moderate anti-proliferation activities at 10 micromol x L(-1) against colon cancer HT-29 and liver cancer HepG2 cell lines.
Aniline Compounds ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Delivery Systems ; Drug Design ; Humans ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; metabolism ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; src-Family Kinases

OBJECTIVETo investigate the basis of distinctive function of acupoint through observing the effects of acupuncture at the areas of acupoint and non-acupoint on functional connectivity of different brain regions.

METHODSTwenty-one healthy volunteers were randomly divided into two groups: 12 cases in the acupoint group and 9 cases in the non-acupoints group. Bilateral Zusanli (ST 36) and its lateral 3-4 mm were punctured with twirling manipulation in the acupoint group and the non-acupoints group respectively. Before and after 25 minutes treatment, data of functional magnetic resonance imaging (fMRI) scanning was taken from bilateral cingulate gyrus (seed point) to analyze the functional connectivity in both groups.

RESULTSBrain functional connectivity was demonstrated widely in both acupoint group and non-acupoint group after acupuncture. Comparing with the non-acupoint group, in the acupoint group, brain functional connectivity with posterior cingulate gyrus was found more intensively in the bilateral tonsil, right dentate nucleus, bilateral uvula, left declive and right tuber of cerebellum, as well as in the left inferior frontal gyrus, right middle temporal gyurs, bilateral paracentral lobule, left cingulate cortex, right superior temporal gyrus, right anterior cingulate gyrus etc., however, its connectivity was less in the bilateral medial frontal gyrus and right inferior frontal gyrus.

CONCLUSIONBoth acupoint and non-acupoint can evoke brain functional connectivity that is similar on the most of regions, but the intensity of this connectivity in the acupoint group is higher than that in the non-acupoint group.

Acupuncture ; Acupuncture Points ; Adult ; Brain ; diagnostic imaging ; physiology ; Brain Mapping ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Radiography ; Young Adult

OBJECTIVETo explore if CHA2DS2 VASc score can predict substrate for persistent atrial fibrillation ( AF) and outcome post catheter ablation of AF.

METHODSFrom January 2011 to December 2012,116 patients underwent catheter ablation of persistent AF in our department and were enrolled in this study. CHA2DS2VASc score was calculated as follows: two points were assigned for a history of stroke or transient ischemic attack and age ≥ 75 and 1 point each was assigned for age ≥ 65, a history of hypertension, diabetes,recent cardiac failure, vessel disease, female. Left atrial geometry ( LA) was reconstructed with a 3.5 mm tip ablation catheter with fill-in threshold 10 in CARTO system. The mapping catheter was stabled at each endocardial location for at least 3 seconds for recording. The electrogram recordings at each endocardial location were analyzed with a custom software embedded in the CARTO mapping system. Interval confidence level (ICL) was used to characterize complex fractionated atrial electrograms (CFAEs) . As the default setting of the software, ICL more than or equal to 7 was considered sites with a highly repetitive CFAEs complex. CFAEs index was defined as the fraction of area of ICL more than or equal to 7 to the left atrial surface. The CFAEs index and outcome of catheter ablation among different CHA2DS2VASc groups were compared.

RESULTSOf the 116 patients, CHA2DS2VASc was 0 in 33 patients, 1 in 31 patients and ≥ 2 in 52 patients. Left atrial surface ((121.2 ± 18.9) cm2, (133.6 ± 23.8) cm2, (133.9 ± 16.1) cm2, P = 0.008), left atrial volume ((103.6 ± 24.8) ml, (118.3 ± 27.8) ml, (120.9 ± 20.9) ml, P = 0.005) and CFAEs index (44.6% ± 22.4%, 54.2% ± 22.2%, 58.7% ± 23.1%, P = 0.023) increased in proportion with increasing CHA2DS2VASc. ICLmax, ICLmin and CFAEs spatial distribution were similar among the three groups. During the mean follow-up of (13 ± 8) months, the recurrence rate were 36.4%, 35.5%, 55.8% among the three groups (P = 0.025).

CONCLUSIONA high CHA2DS2VASc score is associated with extensive AF substrate and higher recurrence rate post catheter ablation of persistent AF.

Aged ; Atrial Fibrillation ; Catheter Ablation ; Electrophysiologic Techniques, Cardiac ; Female ; Heart Atria ; Heart Failure ; Humans ; Hypertension ; Recurrence ; Stroke ; Treatment Outcome

OBJECTIVETo investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions.

METHODSPC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated.

RESULTSIn room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen.

CONCLUSIONUnder hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.

Animals ; Apoptosis ; drug effects ; Cell Hypoxia ; Oxidative Stress ; PC12 Cells ; Propofol ; pharmacology ; Rats ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

BACKGROUNDVitamin D status in relation to pancreatic cancer risks is still inconsistent. This study was performed to evaluate the association between vitamin D status and risk of pancreatic cancer using a meta-analysis approach.

METHODSA systemic review of all relevant literature in English was performed by searching Pubmed, Web of Science and Embase to identify eligible studies from the earliest available date to April 1, 2012. The search terms "vitamin D", "25-hydroxyvitamin D", "pancreatic cancer" or "pancreatic neoplasms" were used to retrieve relevant papers. Inclusion criteria were: (1) the exposure of interest was intake of vitamin D or blood levels of vitamin D; (2) the outcome of interest was pancreatic cancer; (3) data on high and low intake or blood vitamin D in cases and controls were available; (4) odds ratio (OR) estimates with 95% confidence interval (CI) were provided; (5) primary epidemiological data were provided reporting pancreatic cancer incidence. The combined OR values and their 95% CIs were calculated via a meta-analysis. The potential presence of publication bias was estimated using Egger's regression asymmetry test.

RESULTSNine studies with a total of 1 206 011 participants met the inclusion criteria. The test for heterogeneity showed there were significant differences among the included studies (I(2)=70.9%, P=0.001), so a randomized-effects model was used in the meta-analysis. The pooled OR of pancreatic cancer for the highest versus the lowest categories of vitamin D level was 1.14 (95% CI 0.896-1.451), and the Z-score for the overall effect was 1.06 (P=0.288), showing that there was no significant association between vitamin D levels and the risk of pancreatic cancer. Egger's test indicated there was a low possibility of publication bias in this study (P=0.348).

CONCLUSIONDietary vitamin D or circulating concentrations of 25-hydroxyvitamin D are not associated with the risk of pancreatic cancer based on evidence from currently published studies.

Humans ; Pancreatic Neoplasms ; blood ; epidemiology ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood

Objective: To analyze the percentage of myeloperoxidase (MPO)-positive acute myeloid leukemia (AML) blast cells, and to explore the correlation of MPO expression with the clinical features, gene alterations, therapeutic response and prognosis of AML. Methods: The expressions of MPO in BM blasts cells of 233 newly diagnosed AML were retrospectived analyzed, they were divided into two groups using the percentage of MPO-positive blast [low (≤70%) and high (>70%)], clinical features, gene alterations, chemotherapy efficacy and prognosis were compared between the two groups. Results: ①Of the 233 patients, 121(51.9%) were in the low MPO group, and the rest 112(48.1%) in the high MPO group. Favorable-risk group according NCCN guidelines of AML was always MPO-high (χ(2)=32.773, P<0.001), while MPO-low was closely related to poor-risk (χ(2)=7.078, P=0.008); ②DNMT3A mutation (χ(2)=6.905, P=0.009), spliceosome genes mutation (SF3B1/SRSF2/U2AF1) (χ(2)=5.246, P=0.022), RUNX1 mutation (χ(2)=4.577, P=0.032), ASXL1 mutation (χ(2)=7.951, P=0.005) and TP53 mutation (P=0.004) were more likely to be seen in the low MPO group, while C-KIT mutation (χ(2)=8.936, P=0.003) and CEBPA mutation (χ(2)=12.340, P<0.001) were more frequent in the high MPO group, especially CEBPA double mutation; ③The rates of first complete remission in the low MPO group were significantly lower than that in the high MPO group (38.8% vs 68.1%, χ(2)=15.197, P<0.001). Multivariate analysis showed that low MPO positivity significantly affected the CR(1) unfavourably. ④The overall survival (OS) and the progression-free survival (PFS) were significantly worse in the low MPO group (18.0% vs 89.4% for OS, and 11.5% vs 56.7% for PFS, P<0.001). Multivariate analysis disclosed that the low number of MPO was significantly unfavourable prognostic factor. ⑤The low MPO group still showed a worse survival even when restricted to the patients with normal karyotype, the OS and the PFS were 31.1% and 18.8% respectively. Conclusions: AML with different MPO expression percentage had a unique gene mutation spectrum. Low expression of MPO was an independent risk factor for CR(1), OS and PFS in AML patients, which may be a simple and highly significant factor for AML patients when evaluating the therapeutic efficacy and prognosis.
Humans ; Leukemia, Myeloid, Acute ; Mutation ; Peroxidase ; Prognosis ; Remission Induction