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An efficient method for the preparation of polysubstituted gamma-vinyl butyrolactones was developed through gold catalyzed highly diastereoselective cyclization of the malonate substituted allylic acetates.

To investigate the effect of p38 mitogen-activated protein kinase (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of mice with MPTP-induced Parkinson disease (PD).C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immunohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK.The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively (P0.01). In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes (P0.01).P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.

To investigate the effect of phosphorylated-ERK1/2 (p-ERK1/2) on inducible nitric oxide synthase (iNOS) expression in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD), and explore the possible mechanism of dopaminergic (DA) neuron loss in the SN of the midbrain in PD.PD was induced by intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) in C57BL/6N mice, and the behavioral changes of the PD mouse model were observed. Immunohistochemistry and Western blotting were used to detect the number of positive cells and the expressions of tyrosine hydroxylase (TH), p-ERK1/2 and iNOS in the SN of the PD mice, and their changes following Rg1 treatment were assessed.The PD mice exhibited typical symptoms of PD, in which the number of TH-positive neurons and TH expression were significantly reduced by about 77% and 75% (P0.01), respectively, 7 days after the 5th injection of MPTP as compared with those in the control group. Rg1 pretreatment significantly decreased the number of TH-positive neurons and TH expression by 44% and 41% (P0.01), respectively. p-ERK1/2 expression was not observed in the cell nuclei until 1.5 h after the third injection of MPTP, and increased markedly at 6 h. Rg1 pretreatment significantly inhibited the expression of p-ERK1/2 and iNOS (P0.01). A significant positive correlation was noted between the expression of p-ERK1/2 and iNOS (P0.01).P-ERK1/2 may regulate the expression of iNOS to induce DA neuron loss in the SN of PD, and Rg1 may protect the DA neurons possibly by depressing nuclear translocation of P-ERK1/2.

Based on process of fine-blanking, a FE model of fine-blanking is established by using DEFORM-2D software, and the die wear condition is predicted in applying Archard’s wear formula. The developing trend of the die wear and workpiece edge quality are analyzed systematically, as well as the change law of m, Obtained from simulation with different cutting edge model respectively. The obtained results of this research has guiding significance for further standardizing the replacement of the die and then optimizing die structure.

To investigate the role of P38 signaling pathway in modulating the expression of cyclooxygenase-2 (COX-2) in the substantia nigra (SN) of mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD), and explore the possible mechanism of the dopaminergic (DA) neuron death in PD and the effects of ginsenoside Rg1 on the P38 signaling pathway and DA neurons.C57BL6 mice were treated with MPTP to produce the subacute PD model, and the behavioral changes were observed. Immunohistochemistry and Western blotting for tyrosine hydroxylase (TH), COX-2, prostaglandin E2 (PGE2) and phosphorylated P38 (p-P38) were used to observe the changes of positive cell number in the midbrain after treatment with ginsenoside Rg1.Compared with the control mice, the mice with PD presented with typical symptoms of PD. The number of p-P38-, COX-2-, and PGE2-positive cells significantly increased in the SN area 6 h after the 3rd injection of 30 mg/kg MPTP (P0.01). The number of TH-positive neurons in the PD model group was substantially reduced by about 60% (P0.01) in 24 h after the 5th injection of MPTP. In mice with ginsenoside Rg1 treatment, the number of p-P38-, COX-2-, and PGE2-positive cells was reduced obviously 6 h after the 3rd injection of MPTP as compared with that in the model group (P0.01). The number of TH-positive neurons in the SN was decreased by only 30% (P0.01 vs control group) 24h after the 5th injection of MPTP.P38 signaling pathway may play an important role in modulating COX-2 expression in the SN in the early stage of MPTP-induced subacute PD, and ginsenoside Rg1 may act on the P38 signaling pathway to protect the DA neurons in PD.

To assess the iodine status of pregnant women, lactating women and babies and to understand if iodized salt as the main iodine source had met the need of people's demand in regions where iodized salt coverage rate had been over 90%, for the last five years.Pregnant and lactating women, newborns and babies were selected randomly in region where iodized salt coverage rate had been more than 90%, for the five years. Urine iodine levels of pregnant and lactating women, newborns and babies, milk iodine of lactating women and thyroid-stimulating hormone (TSH) of newborns were measured.The median urinary iodine (MUI) of people other than those recently pregnant women, had reached the MUI criterion recommended by WHO with the results as 174.18, 180.37, 147.42, 126.27, 145.26 microg/L, respectively. The percentage of TSH5 pIU/ml of newborns was 14.5%. The median milk iodine of lactating women were in the range of 100-200 microg/L. The percentage of milk iodine150 microg/L of early lactating women was less than that of late lactating women (P0.01). There was a good correlation between urine iodine of babies and milk iodine of lactating women. The abnormal TSH of women was 15.4%. The abnormal TSH mainly existed in women whose urinary iodine level were lower than 150 microg/L.Iodized salt as the main iodine source could basically meet the need of pregnant women, lactating women and babies whose diet structure was simple in the region. However, some people in the area were still under the status of iodine deficiency suggesting that surveillance should be enhanced in people who need more iodine and efficient measures, should be taken.

To investigate the effect of phophorylated c-Jun (p-c-Jun) expression on the expression of COX-2 in the substantia nigra (SN) of the MPTP mouse model of subacute Parkinson disease (PD) and explore the possible mechanism of the dopaminergic (DA) neuron death in PD.C57BL/6N mice were treated with MPTP to establish subacute PD model. The changes of TH-, COX-2- and p-c-Jun-positive cells, and the expression levels of TH, COX-2 and p-c-Jun in the SN in the midbrain were observed with inmmunohistochemistry and Western blotting before and after administration of SP600125, a specific JNK inhibitor.Compared with the mice in control group, the PD mice exhibited typical symptoms of PD. The number of TH-positive neurons and expression level of TH in the model group were significantly reduced in the substantia nigra by about 65% and 75% (P0.001) 7 days after the fifth injection of MPTP. The number of COX-2-immunoreactive cells and the expression level of COX-2 were significantly increased. P-c-Jun was specifically expressed in the nuclei of neurons and p-c-Jun expression level was significantly increased in the SN 6 h after the third injection of MPTP. Double-labeling immunofluorescence assay showed coexpression of COX-2 and p-c-Jun in TH-positive neurons in the SN. In mice treated with JNK inhibitor, the number of TH-positive neurons and TH expression level in the SN was only decreased by 15% and 20% as compared with the control group (P0.001) 7 days after the fifth injection of MPTP, COX-2-positive cell number and COX-2 expression level were obviously reduced as compared with the model group (P0.001), and p-c-Jun was expressed mainly in the cytoplasm of the neurons whose expression level in SN were significantly decreased 6 h after the third injection of MPTP. The PD mice treated with SP600125 showed slight behavioral symptoms.P-c-Jun expression may play an important role in mediating COX-2 expression in the SN in the MPTP model of subacute PD, and inhibiting p-c-Jun activity may provide neuroprotection to the mouse model.

Accumulating evidence implicates activation (phosphorylation) of mitogen-activated protein kinases (MAPK) during nonlethal ischemic preconditioning in the protection of hippocampal CA1 neuron against subsequent ischemic events. In this paper, we undertook to identify the role of extracellular signal regulated kinase (ERK) 5 in cerebral ischemic preconditioning (CIP). Three minutes of ischemia was induced as preconditioning stimulus. Three days later, 6 min of ischemia was induced. The levels of ERK5 protein expression and its activation were detected with or without the CIP in hippocampal CA1 and the dentate gyrus (DG) regions. Our results showed that ERK5 was activated selectively in hippocampal CA1 region with, but not without, the ischemic preconditioning. Notably, during the later phase of reperfusion, the rise in ERK5 activation was strong and persistent with a peak occurring at the third day. The activation peak was effectively prevented and ERK5 protein expression was significantly decreased by intracerebroventricular infusion of ERK5 antisense oligonucleotide (every 24 h for 3 days before the preconditioning), but not by sense oligonucleotide or vehicle. Subsequently, the CA1 neuronal loss was largely elevated. Moreover, both MK801 (10 microM), an antagonist of NMDA receptor, and EGTA (100 mM, but neither 50 nor 150 mM), an extracellular Ca2+ chelator, not only effectively inhibited the ERK5 activation but also markedly abolished CIP-induced survival of the CA1 neurons. These results suggested that activation of the ERK5 pathway by CIP was at least partly dependent on moderate Ca2+ influx via NMDA receptor, which might contribute to ischemic tolerance in hippocampal CA1 region of rats.

To evaluate therapeutic effects of endovenous laser treatment (ELT) and subfascial endoscopic perforator surgery (SEPS) in the treatment of venous leg ulcer (VLU).ELT and SEPS were performed in 10 patients with VLU (involving 10 legs). Among them, external valvuloplasty was performed in 4 legs with deep venous valve insufficiency.Ulcer of the 10 legs healed within 10-60 days after the operation, and follow-up study ranging from 2 to 8 months with the average of 6 months revealed no recurrences.ELT combined with SEPS provides an effective approach for VLU treatment with minimal invasion, and when combined with external valvuloplasty, this approach may effectively reduce ulcer recurrence.

To compare the immediate therapeutic effects of endovenous laser treatment (ELT) and conventional surgery for lower extremity varicosity (LEV).Twenty-two limbs of 20 patients with ELT and 36 limbs of 30 patients with traditional surgery were analyzed in terms of operation time, number of the incision, postoperative pain, complications, postoperative hospital stay and one-year recurrence rate.ELT group had shorter operation time, fewer incisions, less postoperative pain and shorter hospital stay than conventional surgery group, but the two groups showed no significant difference in complications and one-year recurrence rate.As a safe and effective new treatment of LEV with minimal invasiveness and leaving no scars ELT has the potential to replace conventional surgery and extends the surgical indications for LEV treatment.

To investigate the feasibility and accuracy of detection of sentinel lymph nodes (SLN) with combining the dye-directed and radioguided methods in gastric cancer and assess its potential role in determining the rational extent of lymphadenectomy in gastric cancer surgery.Twenty-six patients of gastric cancer diagnosed as T(1)-T(3) were enrolled in this study. Endoscopic injection submucosally of (99m)Tc labeled sulfur colloid solution was performed around the primary tumor 2 - 4 h before operation. Immediately after laparotomy, patent blue violet was injected into subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes or(and) those containing 10 times more radioactivity than surrounding tissue with a gamma probe. Standard radical gastrectomy with lymphadenectomy (D(2) or D(3)) was performed in most of the patients, however, limited surgery was performed in early gastric cancer (EGC) when a rapid frozen examination indicated negative SLNs. All resected nodes were examined postoperatively by routine HE stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining. The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate of regional lymph node status on the basis of SLN status were calculated respectively.SLNs were dectected in 25 of 26 patients with a successful detection rate of 96%. The number of SLNs ranged from 1 to 6, with a mean value of 3.2 per case. The SLNs of gastric cancer were only found in N(1) area in 50% of the cases, and only in N(2) or N(3) in 12%. The incidence of metastasis was significantly higher in SLNs than in non-SLNs (35% vs 7%). The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate were 96%, 94%, 7/8 and 6% respectively. Complete analysis of SLN upstaged 2/7 of patients of gastric cancer.The SLN concept is validated in gastric cancer. Combined-agent SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer and may indicate rational extent of lymphadenectomy for gastric cancer.

To investigate the effects of resuscitation with three different oxygen concentrations on cerebral intra- and extra-cellular calcium, sodium and potassium changes in asphyxiated rat fetuses.Fifty-six fetal rats of gestational age of 20 days were randomly assigned into five study groups: sham operation group (control, n = 11), room-air resuscitation group (n = 10), and 3 oxygen-resuscitated groups (n = 14, 11, and 10 respectively). Different inhaled oxygen concentrations and different timings of oxygen delivery were assigned. Except for control all fetal rats were rendered ischemic and hypoxic in utero by interrupting the placental circulation. After re-circulation, intra- and extra-cellular concentrations of calcium, sodium, and potassium in the brains were measured for each individual group.The mean intracellular free calcium concentration of fetal rat brains was similar for the room-air resuscitation group (552.1 +/- 93.5 nmol/L) and the group resuscitated with 92.8% oxygen (520.6 +/- 79.1 nmol/L) and both were significantly higher than in the control (315.3 +/- 86.9 nmol/L) (P0.001). After resuscitation with 65% oxygen, be it instituted before or immediately after hypoxia, their mean intracellular free calcium concentrations in the brain cells (441.5 +/- 47.9 and 452.9 +/- 36.4 nmol/L respectively) were significantly lower than those in the room-air resuscitation (P0.01) and 92.8% oxygen group (P0.05), though still higher than in the control (P0.05). There was no difference in the total concentrations of calcium, sodium, or potassium among all groups.Resuscitation with 92.8% oxygen or room air exerted a similar effect on the parameters measured, indicating that resuscitation of asphyxiated neonates using 100% oxygen might not be superior to using room air. Resuscitation with 65% oxygen resulted in lower cerebral intracellular calcium concentrations and might produce a better outcome than using 100% oxygen or room air.

ObjectiveTo explore the protective effects of ginseng mixture on myocardial fibrosis (MF) in rats.MethodsA total of 60 Wistar rats were randomly divided into control group without modeling operation, and another 4 groups using subcutaneous injections of isopropyl adrenaline for 10 d to set up the MF model: model group with saline lavage treatment after modeling, captopril group with captopril lavage, ginseng mixture group A and group B with low and high dose mixture treatment respectively. After treatment for 14 d, abdominal aorta and myocardial tissue were extracted to observe the pathological morphological changes and heart weight index in each group.ResultsThe left ventricular weight and heart heavy index of captopril group and group B were significantly lower than that of model group and group A (P