This study is to investigate the effects of sophoridine on NF-kappaB signaling pathway in kidney tissue of endotoxemia mice and the mechanism involved. BALB/c mice were challenged with lipopolysaccharide (LPS) caudal vein injection, then sophoridine was administered by intraperitoneal injection. Totally 50 mice were divided into 5 groups: control group, LPS model group, sophoridine treatment 12 mg x kg(-1) group, 6 mg x kg(-1) group and 3 mg x kg(-1) group. All animals were sacrificed at 6 hours after treatment. Kidney and blood samples were harvested. IKKbeta mRNA and TNF-alpha mRNA expression of renal tissue was measured by the reverse transcription polymerase chain reaction (RT-PCR), and phosphorylation IKKbeta protein (pIKKbeta) was detected by immunohistochemistry. NF-kappaB P65 protein expression and distribution of renal tissue were observed by Western blotting and immunofluorescence laser confocal microscopy. Serum TNF-alpha level was detected by radioimmunoassay. The results showed that the sophoridine significantly reduced the expression of IKKbeta mRNA and pIKKbeta protein, and inhibited the expression of NF-kappaB P65 protein and decreased the entry nuclear rate of NF-kappaB P65 in the renal tissue of endotoxemia mice. Thereby the renal TNF-alpha mRNA expression and serum TNF-alpha level were significantly reduced. These results suggest that sophoridine could inhibit inflammatory reaction induced by LPS through inhibiting activation of NF-kappaB signaling pathway.

Objective To study the anti-oxidative stress effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril(10 mg/kg?d,n=9)or candesartan(4 mg/kg?d,n=9)or combina- tion(Ben:10 mg/kg?d+Can:4 mg/kg?d)for 12 weeks.The tail arterial pressure was measured every two weeks.At end of study,pathological changes in the thoracic aorta,activity of SOD,serum contents of NO and hydroxy radicals,plasma Ang Ⅱ and cGMP,eNOS and P22~(phox)protein expressions in aortic tunica intima were de- termined.Results The thoracic aorta wall was thickened markedly in SHRs,and blood pressure,hydroxy radi- cal,Ang Ⅱ and P22~(phox)protein expression were increased significantly,while the serum NO,level of cGMP and eNOS expression were decreased.Benazepril(Ben)or Candesartan(Can)inhibit the thickening of vessel wall, enhance the activity of SOD(Ben:68.7?2.1,Can:65.6?4.2 vs SHR:48.8?3.2 U/mL,P

OBJECTIVETo investigate the effect of Syk on the VEGF-C expression in breast cancer.

METHODSImmunohistochemical EnVision method was used to detect the protein expression of Syk, NFκB and VEGF-C in breast carcinoma; and the relationship between protein expression of Syk, NFκB, VEGF-C and lymph node metastasis was analysed. MDA-MB-231 cells were transfected with pcDNA3.1(-)-Syk, and the effect of Syk gene on the VEGF-C and NFκB expression was determined.

RESULTSIn the lymph node metastatic group, a lower expression rate of Syk and higher expression rate of VEGF-C and NFκB were detected as compared to the non-metastatic group. The expression of Syk was negatively associated with NFκB (r = -0.448, P = 0.002) and VEGF-C (r = -0.620, P = 0.000) expression, and VEGF-C was associated with the nuclear expression of NFκB (r = 0.310, P = 0.036). Compared with the non-transfected cells, the pcDNA3.1(-)-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA, expression level of VEGF-C protein and NFκB activity (P < 0.05).

CONCLUSIONSSyk may play an important role in the lymph node metastasis of breast cancer. It may down-regulate the expression of VEGF-C by inhibiting the activity of NFκB, which thus suppresses lymph node metastasis of breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Lobular ; genetics ; metabolism ; pathology ; Carcinoma, Medullary ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Genetic Vectors ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; physiology ; Lymphatic Metastasis ; Middle Aged ; NF-kappa B ; metabolism ; Plasmids ; Protein-Tyrosine Kinases ; genetics ; metabolism ; physiology ; RNA, Messenger ; metabolism ; Syk Kinase ; Transfection ; Vascular Endothelial Growth Factor C ; genetics ; metabolism

Objective To explore the clinical value and typing characteristic of prenatal ultrasonography for fetal cystic adenomatoid malformation of the lung(CAML).Methods Ultrasonographic features and typing of fetal CAML in 41 cases detected by prenatal ultrasonography were analyzed retrospectively.All cases were followed up until to the induction of labor or birth.Results (1)Site of tumor: in the 41 cases,there were 22 cases on the left side,15 on the right side and 4 on bilateral.(2)Typing diagnosis of prenatal ultrasonography: three cases were CAML type Ⅰ,14 were type Ⅱ,and 24 cases were type Ⅲ.(3)Pathology diagnosis: thirty two cases were induced abortion.CAML was confirmed in 29 cases by autopsy and the classifications were consistent with the prenatal diagnosis of ultrasonography.Three pulmonary sequestration cases were prenatally misdiagnosed as CAML type Ⅲ by ultrasonography.(4)The other nine cases were followed up to birth.Three masses decreased gradually and then disappeared.Six newborns were confirmed as CAML by CT.Their typings were consistent with the postnatal diagnosis.(5)The diagnostic accuracy rate of prenatal ultrasonography for CAML was 92.7%(38/41).Its misdiagnostic rate was 7.3%(3/41).Conclusions Prenatal ultrasonography has a high accuracy rate for the diagnosis and classification of CAML and is the first choice to detect CAML early in pregnancy.It has an important clinical value.Pulmonary sequestration should be distinguished from CAML type Ⅲ because they tend to be confused.

Objective: To observe the impact of vareniline tartrate on vascular endothelial function and inlfammatory factor releasing in acute coronary syndrome (ACS) patients with nicotine dependence after smoking withdrawal treatment.
Methods: We recruited the in-hospital ACS patients who were smoking ≥10 cigarettes/day for more than 10 years with at least moderate nicotine dependence, and randomly divided them into 2 groups: Varenicline group, the patients received oral medication for 2 weeks and Self withdrawal group, the patients without medication assistance.n=52 in each group. All patients received (10-30) min daily mission and consulting for quit smoking for 2 weeks. The basic information was recorded and blood levels of NO, IL-6 and ET-1 were compared before and after withdrawal treatment.
Results: Compared with they were before, after 2 weeks withdrawal treatment, in Varenicline group, blood levels of ET-1 decreased as (33.950 ± 1.439) ng/L vs (170.198 ± 12.602) ng/L and IL-6 decreased as (0.103 ± 0.020) ng/L vs (0.307 ± 0.051) ng/L; in Self withdrawal group, ET-1 decreased as (60.795 ±7 .036) ng/L vs (170.511 ± 12.374) ng/L, all P<0.05; while NO levels were similar,P>0.05. After treatment, ET-1 level in Varenicline group (33.950 ± 1.439) ng/L was lower than Self withdrawal group (60.795 ± 7.036) ng/L and IL-6 level in Varenicline group (0.103 ± 0.020) ng/L was also lower than Self withdrawal group (0.258 ± 0.042) ng/L, allP<0.05; while NO levels were similar between 2 groups,P>0.05.
Conclusion: Compared with self withdrawal, varenicline tartrate may effectively inhibit inlfammatory factor releasing in ACS patients with nicotine dependence, and therefore improve the vascular endothelial function.

Objective To determine the agreement of interobserver and intraobserver in diagnosing early glaucoma by optic disc morphology,and to explore the efficacy of established methods for evaluating glaucomatous optic discs.Design Prospective study. Participants Clinicians and evaluating methods for glaucomatous optic discs.Methods 120 digital fundus photographs were enrolled including early glaucoma eyes(67 cases)and non-glaucoma eyes but with glaucomatous appearance(53 cases),which were collected in Tongren Hospital.Thirteen ophthalmologists as observers were divided into three groups:GroupⅠ(5 clinicians)were trained with stan- dardized methods for evaluating glaucomatous optic disc damage recently.GroupⅡ(4 clinicians)were ophthalmologists majoring in glaucoma.GroupⅢwere ophthalmologists not specializing in glaucoma.In general groupⅡandⅢ,none had been trained with the es- tablished criteria.Observers evaluated the photos 3 times,with an interval time of 3 days.Kappa statistics were used to evaluate agree- ment between the intraobserver and interobserver.Main Outcome Measures Interobserver and intraobserver agreement,kappa value. Results In GroupⅠ,4 clinicians were in almost perfect agreement,1 clinician was in substantial agreement,kappa value ranging from 0.779(90.0%)to 0.966(98.3%).In GroupⅡ,almost perfect agreement occurred in 2 clinicians,substantial in 1 clinician and moderate in 1 clinician,kappa value ranging from 0.506(82.5%)to 0.866(93.3%).In GroupⅢ,the agreements in 4 clinicians were substantial, moderate,fair,and slight,respectively,kappa value ranging from 0.094(54.2%)to 0.778(89.2%).In term of interobserver agreement for glaucoma diagnosis,kappa values in GroupⅠranged from 0.768 to 0.983,in GroupⅡ0.354-0.834,in GroupⅢ0.335-0.737,respec- tively.Conclusions Intraobserver and interobserver agreement rates in early glaucoma diagnosis are substantially improved through training on optic disc morphologic evaluation methods.Establishing the diagnosis criteria for glaucomatous optic disc damage can raise the correct rate of diagnosis.

Objective To compare the predictive value of 5 scoring systems for hemorrhagic transformation risk after intravenous thrombolysis in patients with acute ischemic stroke (AIS) in different therapeutic windows.Methods A single-center and retrospective study was performed for 243 AIS patients who underwent intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in different therapeutic windows in our department during January 2014 and December 2016.Five scoring systems,including HAT model (hemorrhage after thrombolysis),MSS model (multicenter stoker survey),GRASPS model (glucose at presentation,race,age,sex,systolic blood pressure at presentation,severity of stroke at presentation),SEDAN model (baseline blood sugar,early infarct signs,hyperdense cerebral artery sign on admission CT,age,NIHSS on admission),and SITS model (safe implementation of thrombolysis in strokemonitoring study) were used to evaluate the risks for hemorrhagic transformation.The relationships between the 5 scoring systems and incidence rate of hemorrhagic transformation were analyzed among the patients in different therapeutic windows.The predictive values of the 5 scoring systems were compared using the areas (AUC) under the receiver operating characteristic (ROC) curve.Results When the AIS patients were treated by intravenous thrombolysis within 3 h,the AUC of GRASPS and HAT models were 0.698 and 0.619,respectively,higher than those of the other 3 systems.When the therapeutic window was between 3 to 4.5 h,HAT model and SEDAN model had highest AUC (0.719,0.744) than the other 3 systems (P ＜0.05).When the windows were ＞4.5 ～6 h,the HAT model had the highest AUC (0.676).Conclusion The 5 scoring systems show better predictive value for hemorrhagic transformation after intravenous thrombolysis.For the therapeutic window within 4.5 h,HAT model presents best predictive value than the other 4 scoring systems.

Objective To summarize the features of esophageal hiatus hernia (EHH) on contrast-enhanced ultrasound (CEUS) and investigate the diagnostic value of CEUS in EHH.Methods A retrospective analysis of 88 EHH patients and 50 healthy controls was conducted with focus on their findings on CEUS.Results The structures of the cardiac and abdominal esophagus were clear in 50 healthy controls,and the esophageal hiatus diameters were (1.96±0.39) cm.In contrast,the cardiac and abdominal esophagus in EHH patients were unable to be identified in subdiaphragm region.The esophageal hiatus was wider with a diameter of (3.24±0.76) cm.The difference was statistically significant(t=2.36,P＜0.05).The hernia sacs were found in 78 EHH patients at rest.And the hernia sacs were present on the diaphragm in 10 EHH patients after pressure.The maximum diameter of hernia sac was 7.6 cm.The size of hernia sac may change with abdominal pressure.In sliding EHH patients,the sac wall was found to slide up and down the diaphragm.A mass was found on the wall in 2 patients.The B ring was present in 76 patients.For healthy controls in supine position,contrast-enhanced ultrasound showed that the gastric bottom and diaphragm were at dependent or horizontal position.The gastric bottom and diaphragm was upward in 73 patients.Conclusions The EHH has characteristic appearance on CEUS.It is easy to detect and diagnose EHH with CEUS,which has a diagnostic value in detection of space-occupying lesions in hernia sac.CEUS can be used for EHH screening.

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; pharmacology ; Drug Carriers ; chemistry ; Female ; Liposomes ; chemistry ; Male ; Mice ; Nanoparticles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacokinetics ; pharmacology ; Particle Size ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma 180 ; pathology ; Silicon Dioxide ; chemistry ; Tumor Burden ; drug effects

BACKGROUND: Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration (CVVH). Hence blood hemoperfusion with resin adsorption combined CVVH (HP+CVVH) has higher ability of mediator clearance, and can improve clinical outcomes in theory. This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration (HP+CVVH) on plasm cytokines like TNF-α, IL-1β, IL-6, cellular immunity and prognosis in patients with multiple organ dysfunction syndrome (MODS). METHODS: This was a prospective, randomized clinical trial. A total of 30 patients who had been diagnosed with MODS were enrolled in this study. Patients were randomly allocated to routine treatment+HP+CVVH group (treatment group) and routine treatment+only CVVH group (control group). In the treatment group, patients received blood hemoperfusion with resin adsorption for 2 hours, and then received CVVH for 10 hours every day. In the control group, patients received CVVH for 12 hours only every day. The patients in the two groups received blood purification therapy for three days. The plasma of patients in the treatment group was obtained at 0, 2, 12, 24, 26, 36, 48, 50, 60 hours, 5th day, 7th day and 10th day, respectively. The plasma of patients in the control group was obtained at 0, 12, 24, 36, 48, 60 hours, 5th day, 7th day and 10th day, respectively. APACHE II score, T-lymphocytes subpopulations, blood lactate acid concentration, heart rate, breathing rate, and oxygenation index were observed. RESULTS: Plasma cytokines like TNF-α, IL-1β, IL-6 decreased markedly after HP (P<0.01);T-lymphocytes subpopulations CD3+, CD4+, CD8+, CD4+/CD8+ increased after HP+CVVH or only CVVH. The plasma concentrations of TNF-α, IL-1β and IL-6 in the two groups were not markedly different at 12, 36, and 50 hours. But on the 5th day, the plasma concentrations of TNF-α, IL-1β and IL-6 in the treatment group were lower than those in the control group (P<0.05). On the 28th day, 5 patients died in the treatment group, and 6 patients in the control group. CONCLUSIONS: Both HP+CVVH and CVVH can clean plasma cytokines like TNF-α, IL-1β, and IL-6, and improve cellular immunity and clinical symptoms and signs of patients. Compared with only CVVH, the plasma concentrations of TNF-α, IL-1β and IL-6 were lower on the 5th day, and patients have an increased survival rate on the 28 day in the HP+CVVH group.