Objective To explore the mechanism of HMGB1 and TLR4 in pancreatic tissue of rats with severe acute pancreatitis and the intervention effect of Ulinastatin .Methods The 54 SD rats were completely random divided into control group ,SAP group and Ulinastatin treatment group ,and each group was divided into three groups :6 ,12 h and 24 h groups (each group n=6) .In con‐trol group ,we turned the pancreatic tissue ,in SAP group ,the SAP model was made with 5% taurocholic acid ;and in the treatment group ,and intravenous injection of ulinastatin was conducted after the SAP model was successfully made .Then we observed the pancreatic tissue pathology in the three groups .The amylase in serum was detected by EPS‐G7 assay ,the HMGB1 in serum and pancreatic tissue was detected by ELISA assay ,the expression levels of HMGB1 and TLR4 in pancreatic tissue were detected by Envision two‐step immunoassay .Results Compared with control group ,the amylase of each time point in SAP group and treatment group were significantly higher ,and the pathology changed obviously (P<0 .05) ,and the SAP model was successfully made .The HMGB1 expression in pancreatic tissue and serum started increase at 6 h ,increased quickly at 12 h and maintained the increasing trend to 24 h in SAP group and it was significantly higher at the same time point compared with that of control group (P<0 .05);at the same time point ,the HMGB1 in treatment group was significantly lower than that of SAP group (P<0 .05);in SAP group , the expression of TLR4 in pancreatic tissue started increasing at 6 h ,reached its peak at 12 h and started decreasing at 24 h ,it was significantly higher than the control group at the same time point (P<0 .05) .At the same time point ,the TLR4 was significantly lower in the treatment group than SAP group (P<0 .05) .Conclusion The proinflammatory effect of HMGB1 in SAP rats pancre‐atic could be partly combine its receptor TLR4 and MyD88‐dependent pathway through implementation ,and the protecting mecha‐nism of Ulinastatin could be interrupt the HMGB1 and TLR4 signaling pathway in SAP rats pancreatic tissue .

Descending activation pathways in spinal cord are essential for inducing and modulating autokinesis, but whether the effects of general anesthetic agents on the descending pathways are involved in initiation of skeletal muscle relaxation or not, as well as the underlying mechanisms on excitatory amino acid receptors still remain unclear. In order to explore the mechanisms underlying etomidate's effects on descending activation of spinal cord motoneurons (MNs), the conventional intracellular recording techniques in MNs of spinal cord slices isolated from neonatal rats (7-14 days old) were performed to observe and analyze the actions of etomidate on excitatory postsynaptic potential (EPSP) elicited by electrical stimulation of the ipsilateral ventrolateral funiculus (VLF), which was named VLF-EPSP. Etomidate at 0.3, 3.0 (correspond to clinical concentration) and 30.0 µmol/L were in turn perfused to MN with steadily recorded VLF-EPSPs. At low concentration (0.3 µmol/L), etomidate increased duration, area under curve and/or half-width of VLF-EPSP and N-methyl-D-aspartate (NMDA) receptor-mediated VLF-EPSP component (all P < 0.05), as well as amplitude, area under curve and half-width of non-NMDA receptor-mediated VLF-EPSP component (all P < 0.05), or decreased amplitude and area under curve of VLF-EPSP, its NMDA receptor component, and non-NMDA receptor component (all P < 0.05). However, at 3.0 and 30.0 µmol/L, it was only observed that etomidate exerted inhibitory effects on amplitude and/or duration and/or area under curve of VLF-EPSP (P < 0.05 or P < 0.01) with concentration- and time-dependent properties. Moreover, NMDA receptor-mediated VLF-EPSP component was more sensitive to etomidate at ≥ 3.0 µmol/L than non-NMDA receptor-mediated VLF-EPSP component did. As a conclusion, etomidate, at different concentrations, exerts differential effects on VLF-EPSP and glutamate receptors mediating the synaptic transmission of descending activation of MNs in neonatal rat spinal cord in vitro.
Anesthetics, Intravenous ; pharmacology ; Animals ; Animals, Newborn ; Efferent Pathways ; physiology ; Electric Stimulation ; Etomidate ; pharmacology ; Excitatory Postsynaptic Potentials ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Motor Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects ; physiology ; Spinal Cord ; physiology

OBJECTIVETo evaluate clinical outcomes of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction under arthroscopy and repair of the injured posteromedial complex structure of the knee joint in the treatment of posterolateral knee dislocation with multiple ligament injuries.

METHODSFrom March 2008 to August 2012,22 patients (16 males and 6 females, ranging in age from 20 to 53 years old, with an average of 30.5 years old) with posterolateral dislocation of the knee were treated with primary reconstruction of ACL and PCL, combined with the repair of injuries in the posteromedial complex and soft-tissue. Eight patients had injuries caused by sports,5 patients road accidents and 9 patients falling down. The ACL was reconstructed using the gracilis and semitendinosus tendons. The PCL was reconstructed using LARS artificial ligaments (14 cases), or gracilis and semitendinosus tendons (8 cases). Suture repair was performed in 17 patients with posteromedial ligament injuries,and self-semitendinosus strengthening operations were performed in 5 patients. Continuouspassive montion (CPM) and active exercises were executed after operation at early stage. The IKDC and Lysholm system were used to evaluate therapeutic effects.

RESULTSAll the patients were regularly followed up, and the duration ranged from 11 to 56 months (averaged, 39 months). According to the IKDC scale,9 patients got a grade A result, 10 got a grade B result, and 3 got a grade C result. The IKDC subject score was 89.6±3.1 and the Lysholm scores was 90.7±1.8 at the latest follow-up, which were both better than those before operation.

CONCLUSIONReconstructing the ACL and PCL and repairing injured posteromedial complex of the knee followed by an active rehabilitation is an effective method to treat posterolateral knee dislocation.

Adult ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Injuries ; Arthroscopy ; methods ; Female ; Humans ; Knee Dislocation ; surgery ; Male ; Middle Aged ; Posterior Cruciate Ligament ; injuries ; surgery ; Reconstructive Surgical Procedures ; methods

AIM: To investigate the change of myopic choroidal neovascularization treated by ranibizumab and evaluate their value in monitoring the effect of anti-vascular endothelial growth factor ( VEGF) therapy. ·METHODS: The study enrolled 30 patients ( 30 eyes ) diagnosed with myopic choroidal neovascularization. All affected eyes were treated with intravitreal ranibizumab 0. 05mL ( 10mg/mL ). Best corrected visual acuity ( BCVA ) , non-contact tonometer, ophthalmoscope, fundus fluorescein angiograph ( FFA ) and OCTA were evaluated monthly until 6mo. The changes of BCVA and central macular thickness ( CMT) were compared at 1, 3 and 6mo after treatment. ·RESULTS:All patients received an average of 1. 70±0. 65 injections. BCVA was 0. 96 ± 0. 17 ( LogMAR ) before therapy, and BCVA 1, 3 and 6mo after treatment respectively improved by 0. 23 ± 0. 09, 0. 34 ± 0. 07, 0. 38 ± 0. 11. The differences were significant ( t=5. 461, 8. 191, 8. 894; P<0. 05 ). Mean CMT decreased form 281. 07 ± 13. 72μm to 261. 33 ± 13. 13μm, 243. 47 ± 16. 65μm, 234. 73 ± 17. 52μm respectively 1, 3 and 6mo after treatment, showing significant differences (t=12. 007, 13. 360, 9. 531;P<0. 05). OCTA revealed a progressively smaller vascular lesion and reduction in capillary density. · CONCLUSION: Intravitreal ranibizumab for CNV secondary to pathologic myopia is effective and safe;OCTA is a noninvasive and time-saving new technology, and it also is a promising tool for clinicians to make preliminary diagnosis and assess treatment efficacy in the follow-up visits.

The study evaluates the lipolysis rate and extent of type Ⅲ lipid formulations using testosterone undecanoate as a model drug after digestion with in vitro lipolysis model, and studies the digestive regularity with optical microscope and electrical conductivity. The results showed that for testosterone undecanoate type Ⅲ lipid formulations with castor oil as oil phase and Transcutol HP as latent solvent, the lipolysis rate and extent were increased with the increase of oil phase proportion and were decreased with excessive proportion of surfactant, in which can see liquid crystal phase during lipolysis process. The lipolysis rate of type ⅢB lipid preparations with different surfactant were ordered as Labrasol > Tween 80 > Cremophor EL, but the rate of type ⅢA is different in quick digestion phase and slow digestion phase. The lipolysis extent of type Ⅲ lipid formulations with different surfactant were ordered as Cremophor EL > Tween 80 > Labrasol. These may be related to the digestive effect of pancreatic lipase on different surfactants. This study implied that the lipolysis rate and extent of type Ⅲ lipid formulations are greatly influenced by the proportion of oil phase and surfactant, and the surfactant structure. These factors will affect the in vivo digestion and should be taken into account when screening type Ⅲ lipid formulations.

By functional plates,16 strains which can produce?-mannana-se were isolated frnm 28 Bacillus spp.Using a pair of degenerated primers,the conserved fragments of?-mannanase gene from the selected strains were amplified by PCR.The obtained nucleotide fragments were sequenced and compared with the homologous?-mannanase genes in GenBank and a phylogenetic tree was generated.Comparing to the genes coding?-mannanase published,the cloned nucleotide fragments show the highest sequence identity between 62% and 98%.The genes coding fnr?-mannanase of Bacillus circulus have low identity while the?-mannanase genes of Bacillus subtilis and other Bacillus spp. have high identity.

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.

0.05),which were (5.64?2.00)d in single-circle group,(5.80?3.74)d in double-circle group,(6.22?2.76)d in triple-circle group.According to the treatment effects,CEA value decreased during pre-and post-neoadjuvant chemotherapy in each groups(P0.05).Through our survey,used different neoadjuvant chemotherapy circle,patients in single-circle group and double-circle group were completely accepted within full confidence;but receptance of strategy in triple-circle group was 66.7 %(12/18).All operations were suc- cessful.The difference of postoperative aerofluxus time between single-circle group and double-circle group had sta- tistical significance(P0.05).Conclusion Analyzing neoadjuvant chemo- therapy circles,time between neoadjuvant chemotherapy and operation,treatment effect and operation results,it is a feasible and secure colorectal cancer multi-discipinary strategy for patients in West China that choose the treatment of neoadjuvant chemotherapy with double-circle and short preparation time.

AIM:To be one of the primary cause injury to multiple sites of ocular of glaucoma which affects over 70 million people worldwide. We applied data mining techniques, linear and the matrix operations, efficiently calculated the network and estimated the possible function of the“node” genes of the retina and optic of glaucoma, in order to provide new thought and method on the pathogenesis of glaucoma.
METHODS: The data in this study is from Gene Expression Omnibus ( GEO ) which belong to Nation Center for Biotechnology Information ( NCBI) , the quality of the raw data CEL files was processed and analyzed by the Expression software which belong to Affymetrix Inc. , Santa Clare, CA, USA. Significant analysis method ( SAM) which base on the T test was used to identified the significant genes. Based on GRNInfer and Gvedit soft we set up gene networks of optic and retina of mice and further more enriched analysis which based on DAVID and MAS3. 0 online software were processed.
RESULTS:The analysis between the group of the optic nerve heads and retinas in different stage of glaucoma showed that the amount of significant different expressed genes in the optic never head group increased significantly comparing with the group of retina in the early stage of glaucoma, the analysis of the genes network construction show that:the node genes of optic nerve heads included Unc13c、Kif5a、TRPM1、PANX; and the node genes of retina include POU4F1, NEFL, BC03870, CALB2. Metabolic pathways enrichment analysis which based on MAS3. 0 online platform show that there was mainly the amyotrophic lateral sclerosis, tyrosine metabolism, melanogenesis, Nitrogen metabolism, Gap junction, Leukocyte transendothelial migration metabolism pathway enriched out in optic nerve head; and there was mainly amyotrophic lateral sclerosis, neurodegenerative disorders, prostate cancer, leukocyte transendothelial migration metabolism pathway enriched out in retina.
CONCLUSION:By understanding bioinformatics result, it seems optic were more sensitive than the retina to high intraocular pressure, and weather high expression of TYrp1 gene can be as a sensitive diagnostic item require more evidence back up. Functional enrich analysis of node gene showed that cytoskeleton reconstructed, molecular motor and nutrients transport function improve in optic; and in retina, the most prominent finding in retina was enrichment function modules were focus on regeneration, repairing and differentiation of cells, which remind that we should reinforce research on reparation of retina of primary glaucoma. Metabolic pathways enrichment analysis show that inflammatory response plays prominent place in optic and retina of primary glaucoma, because of the optic narrow and crowed anatomic shape, nutrient metabolism and substances transfer enrichment modules play an important role in optics of primary glaucoma.

Borneol is a traditional Chinese medicine. In the past few years, many studies showed that borneol can improve the bioavailability of other drugs, promoting drugs to cross the blood-brain barrier, so the potential drug interactions between borneol and other medicines have attracted great attention, but the influence of borneol to CYP450 and its isoforms are rarely reported. In this research, male Wistar rats were orally administered by borneol for 7 days, then the mRNA and protein expression and the activities of CYP2D were detected, we also compared the pharmacokinetic parameters of CYP2D's specific substrate between control group and borneol group. The results show that borneol (33, 100 and 300 mg x kg(-1) x d(-1)) have no significant effect on CYP2D, while the activites of CYP2D increased 1.71, 1.97 and 2.89 times comparing to the control group. At the same time, borneol (300 mg x kg(-1) x d(-1)) caused the C(max) decreased 10.6% (P > 0.05), AUC(0-∞) decreased 27.5% (P < 0.01), CL/F increased 41.1% (P < 0.01), V(z)/F increased 23.1% (P > 0.05) of dextromethorphan. Our data provided that borneol speed up dextromethorphan's elimination in vivo. Since the activity of CYP2D can be induced by borneol, the metabolic interactions might happen when borneol and the substrate drug CYP2D are used together.
Animals ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Blood-Brain Barrier ; Bornanes ; pharmacology ; Cytochrome P-450 Enzyme Inducers ; pharmacology ; Dextromethorphan ; Drug Interactions ; Liver ; drug effects ; enzymology ; Male ; Medicine, Chinese Traditional ; RNA, Messenger ; Rats ; Rats, Wistar