Objective To investigate the effect of isosorbide mononitrate on the levels of NO,iNOS,IL-1 and IL-6 in lung tissue of spontaneously hypertensive rats (SHR).Methods Fourteen-week-old Wistar and SHR male rats were randomly divided into the W0,W1,S0 and S1 group,with 10 rats ineach group.Rats in the W0 and S0 group were fed with the normal saline and the ordinary food,rats in the W1 and S1 group were fed with isosorbide mononitrate and the ordinary food.Twelve weeks later,levels of NO,iNOS,IL-1 and IL6 in rat lung tissue were detected.Results Compared with the W0 group,levels of NO,iNOS,IL-1 and IL6 were significantly increased in the W1 groups (P ＜ 0.05,respectively).Compared with the SO group,levels of NO,iNOS,IL-1 and IL6 were significantly increased in the S1 group (P ＜ 0.05,respectively).In the W1 and S1 group,levels of iNOS and NO were positively correlated with IL-1 and IL-6.Conclusion 1.Isosorbide mononitrate may lead to increases of NO,iNOS,IL-1 and IL6 in lung tissue of Wistar rats,which indicates the presence of chronic inflammation.2.Longterm feeding of isosorbide mononitrate may lead to increases of inflammatory factors in SHR rats,contributing to the inflammatory state in rats.

Objective To explore the effects of repetitive transcranial magnetic stimulation on behaviors and hippocampus neuronal apoptosis in rats with chronic stress-induced depression.Methods 40 male SD rats of SPF grade were randomly divided into normol control group (n =8) and model preparation group (n =30) after screening.Rats in model preparation group were singly housed and given chronic unpredictable mild stress(CUMS) to build depression model.Excluding unsuccessful modeling rats,the model preparation group was divided into three groups:model group(n=8,without any treatment),rTMS group (n=8,with the intervention of 10 Hz rTMS) and shame group (n=8,simulation of rTMS environment without rTMS stimulus).The changes of behaviors in each group were detected by weight measurement,sucrose consumption test and open-field test.The changes of morphology of hippocampal neurons were detected by Nissl's staining.The changes of Bax in hippocampal neuron were detected by Immunohistochemical staining.Results (1) Behavioral results showed stress for 21 d could make rat behavior scores decrease significantly(all P＜0.05),and rTMS intervention could significantly improve their behavior scores (all P＜0.01).Compared with model group,the weight reduction rate (0.32±0.05)％,the score of sucrose consumption test(7.03 ± 1.02) and the score of open field test(8212.41 ± 1416.15,8.75 ± 1.58) in rTMS group was higher(P ＜0.01).(2) Nissl staining showed stress for 21 d could make the number of hippocampal CA3 neurons was reduced,cell morphology was poor,and the number of Nissl bodies was reduced.rTMS intervention could increase the number of hippocampal CA3 neurons,cell morphology was integral and the number of Nissl bodies was increased.(3) Immunohistochemistry results showed stress for 21 d could cause the number of Bax cell were significantly increased(P＜0.01),and rTMS intervention can make the number of Bax cell were significantly lower(P＜0.01).Conclusion rTMS intervention improves the depressive behavior in chronic stress depression model rats and inhibits the apoptosis,which might work through inhibition of neuron apoptosis and decline of Bax expression in hippoeampal neurons.

Objective To explore the effect of different temperature of the forced- air warming system on the prevention of hypothermia during laparotomy of infants. Methods A total of 60 infants undergoing laparotomy under general anesthesia were recruited and divided into three groups by random digits table method with 20 cases each according to admitting time; when used the force- air warming system intraoperatively, the three groups were respectively setting on 45℃(automatic adjustment for 43 ℃ after 45 minutes), 43 ℃ and 38 ℃.The core temperature were respectively recorded before anesthesia and 15, 30, 45, 60 minutes after anesthesia (every 30 minutes after 1 hour).The hypothermia incidence and anesthesia recovery conditions were recorded simultaneously. Results There was no significant difference on the core temperature among three groups before anesthesia (P > 0.05). 30 minutes after the anesthetic, the core temperature of 45 ℃ group was (36.31±0.20) ℃,43 ℃ group was (36.32±0.24) ℃ and 38 ℃ group was (36.08±0.21) ℃.The differences among three groups was statistically significant (F=8.12, P < 0.01), but there was no significant difference between 45 ℃ group and 43 ℃ group (P > 0.05). 60 minutes after the anesthetic, the core temperature of 45 ℃ group was (36.39±0.26) ℃,43 ℃ group was (36.19±0.22) ℃ and 38 ℃ group was (35.92±0.15) ℃. The differences among three groups was statistically significant(F=25.19, P<0.01).The hypothermia incidence of 45℃group, 43℃ group,38℃ group was 10.0%(2/20), 25.0%(5/20), 50.0%(10/20)respectively and the differences among three groups was statistically significant( χ2=8.04, P<0.05). The time to complete consciousness of 45 ℃ group was (15.40±5.09) minutes,43 ℃ group was (19.80±4.10) minutes and 38 ℃ group was (22.00±4.36) minutes. The differences among three groups was statistically significant (F=10.96, P<0.01). The time to tracheal extubation of 45 ℃ group was (18.10±5.97) minutes, 43 ℃ group was (21.85±4.02) minutes and 38 ℃ group was (24.90±5.54) minutes.The differences among three groups was statistically significant (F=9.83, P<0.01). Conclusions The forced-air warming system can increase the infants′peripheral tissue heat content and reduce the heat losing.So that it will help decrease the intraoperative hypothermia incidence and shorten the anesthesia recovery period.Meanwhile the higher temperature of the forced-air warming system is setted ,the better effect it is.

Objective To explore the effects of hydrogen sulfide (H2S) on neuron specific-enolase (NSE),neurotrophic protein S100B and neurons apoptosis in hippocampus CA1 region in the early stage of cardiopulmonary resuscitation (CPR) in rabbits. Methods Twenty-five Japanese white rabbits were randomly divided into three groups:sham group (S group),cardiac arrest group (CA group) and H2S treatment group (H2S group). Rabbits were anaesthetized with 5％ halothane,trachea was exposed and intuhated,right femoral vein was cannulated for medical agent administration,and right carotid artery was cannulated for monitoring of blood pressure and blood samples taken. Cardiac arrest was produced by suffocation with clamping the endotracheal tube and turning off mechanical ventilation.Mter 8 min of the endotracheal tube clamping, rabbits received CPR. After the restoration of spontaneous circulation (ROSC),rabbits in groups CA and H2S inhaled 30％ O2 or 30％ O2 containing 80 × 10-6 H2S,respectively.Blood samples were taken before,and 30 min and 60 min after ROSC for detection of the concentrations of NSE and S100B in the plasma. As 60 min after ROSC,rabbits were decapitated after perfusion with 500 ml phosphate-buffered saline and followed by 4％ paraformaldehyde 500 ml through aortic artery,and then the hippocampus was removed rapidly and fixed in 4％ paraformaldehyde for the histological examination.All values were expressed in mean ± standard deviation ((x) ± s).Comparisons were carried out among different groups with SNK-q test of one-way analysis of variance ( One-Way ANOVA plus SNK).Results In comparison with group S,the concentrations of NSE and S100B were significantly increased 30 min and 60 min after ROSC (P ＜ O.05),the viable neurons were decreased and cleaved caspase-3 positive neurons in hippocampus CA1 region increased 60 min after ROSC in groups CA and H2S (P ＜0.05).In comparison with group CA,the concentration of S1OOB decreased 60 min after ROSC (P ＜ 0.05) ; the viable neurons were increased while cleaved caspase-3 positive neurons in hippocampus CA1 region decreased 60 min after ROSC in group H2S ( P ＜ 0.05 ). Conclusions H2S can inhibit the neurons apoptosis in hippocampus CA1 region,increase the viable neurons,decrease the concentration of S100B in the plasma,and then attenuate the cerebral injury after cardiopulmonary resuscitation in rabbits.

Objective To knockout Rag2 and IL2rg genes and construct severe combined immunodeficiency mice based on CRISPR/Cas9 technology. Method Design and synthesis of 25 bp sgRNA were made according to the Rag2 and IL2rg sequences in Genbank. After annealing, sgRNA was cloned into pX330 vector. Recombination plasmid Rag2?sgRNA, IL2rg?sgRN and Cas9 were then transcribed into RNA, these RNA were microinjected into zygotes and the zygotes were transplanted into recipient ICR mice. F0 founders were born and mutated F0 founders mated with wild type mice to obtain F1 generation heterozygous mice. Mutated F1 mice were crossed and got F2 generation homozygous mice. Genotype and phenotype of the knockout mice were identified by sequencing, flow cytometry and xenograft model. Results Rag2?sgRNA and IL2rg?sgRNA recombination plasmids were constructed and transcribed into RNA. After microinjection and mat? ing, F0 founders were born and F2 homozygous mice were obtained. The results of sequencing showed that there were two types of genotype in IL2rg gene, 10 bp or 11 bp deletion;however, there was only one genotype in Rag2 gene, which was 8 bp deletion. Compared with wild?type BALB/c mice, the number of CD3 +, B220 + and NKp46 + cells in peripheral blood of the knockout mice was reduced significantly. After inoculation of human breast cancer cell line SKBR?2HL cells, tumor size in the xenograft mouse model was increased gradually along with time extension. Conclusion CRISPR/Cas9 is an efficient way to mutate Rag2 and IL2rg gene in mice in vivo, leading to aberrant T cells, B cells and NK cells.

To build the Dendrobium nobile -T2DM network, and elucidate the molecular mechanism of D. nobile to type 2 diabetes (T2DM). Collect the chemical composition of D. nobile and the targets on T2DM by retrieving database and documents, build the network of D. nobile to T2DM using the entity grammar systems inference rules. The molecular mechanism of D. nobile to T2DM includes: (1) regulating lipid metabolism by lowering triglyceride; (2) reducing insulin resistance; (3) protecting islet cells; (4) promoting the glucose-dependent insulin tropic peptide (GIP) secretion; (5) inhibiting calcium channel. Under the guidance of network pharmacology, through entity grammar systems inference rules we elucidate the molecular mechanism of D. nobile to T2DM, and provide the basis for the further development of health care products based on D. nobile.
Animals ; Calcium Channels ; genetics ; metabolism ; Databases, Factual ; Dendrobium ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hypoglycemic Agents ; administration & dosage ; chemistry ; Insulin Resistance ; Islets of Langerhans ; metabolism ; Triglycerides ; metabolism

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.
Administration, Cutaneous ; Animals ; Coumaric Acids ; administration & dosage ; pharmacokinetics ; Male ; Needles ; Rats ; Rats, Sprague-Dawley ; Skin Absorption

Objective To observe the effect of DPC4 gene transfection on the chemotherapy sensitivity of pancreatic carcinoma cells. Methods The human DPC4 complementary DNA was subcloned to the retroviral vector pLXSN to obtain recombinant pLXSN/DPC4 with direct inserting potential. The daughter cell BxPC-3/DPC4 which had DPC4 stable expression was acquired after the pancreatic carcinoma BxPC-3 cells had been transfected with pLXSN/DPC4. The sensitivity of the carcinoma cells for 5-Fu and gemcitabine was observed. Meanwhile, the mRNA level of Mdr-1 and Chk1was detected by semi-quantity PCR assay. Results The 50% inhibiting concentrations (IC50)of 5-Fuand gemcitabin4e for BxPC-3 (culturing for 72 h) were rather lower than those of BxPC-3/pLXSN and BxPC-3/-cells. Moreover, the semi-quantity PCR assay revealed that the mRNA level of Mdr-1 and Chk1 was down-regulated. These findings indicated that pLXSN/DPC4 vector, 5-Fu and gemcitabine could inhibit the growth of pancreatic cancer cells. The combined therapy with pLXSN/DPC4 vector and chemotherapeutic drugs could further inhibit the growth of cancer cells. Conclusion The DPC4 gene transfection could enhance the sensitivity of pancreatic cells to chemotherapy, which may be realized through the down-regulation of Mdr-1 and Chk1 gene expression.

Two γ-glutamyl-cysteine peptides (γ-GCPs ) , ( SC2 RC7 )-γ-L-glutamyl-S-allyl-L-cysteine ( 1 ) and ( SC2 RC7 )-γ-L-glutamyl-S-propyl-L-cysteine ( 2 ) have been isolated from fresh garlic scales using ion-exchange chromatography and pre-HPLC. Their molecular structures were identified by HPLC-MS, CD, 1 H NMR, 13 C NMR, specific rotation and confirmed by the corresponding standard compounds. The influence of exogenously adding 1 and 2 on the bioavailability of iron and zinc from food legume was examined with soybean and mung bean, in the level of 0. 01 mmol/5 g of legume respectively. The enhancing effect of the two γ-GCPs of compound 1 and 2 on bioaccessibility of iron was generally evidenced in the case of soybean ( from 1 . 88% to 6 . 73% and 4 . 42%) and mung bean ( from 2 . 52% to 12 . 04% and 9 . 38%) . The two γ-GCPs similarly enhanced the bioaccessibility of zinc from the food legume, in soybean ranging from 13. 37% to 23. 95% and 20. 58%, and in mung bean from 15. 98% to 28. 44% and 27. 05%. Thus, both compounds 1 and 2 obviously had a promoting influence on the bioavailability of iron and zinc from food legumes. These findings are of practical value in a food-based strategy to enhance the bioavailability of trace minerals for human health.

Objective To study the changes and mechanism of the function of islet βcells and insulin signal transduction molecules in rats after long-term period lipid infusion.Methods Thirty SpragueDawley (SD) rats were randomly divided into free fatty acid (FFA) and normal saline (NS) groups.Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery.A technique for a 72-h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion.The infusion period was started on day 2 after surgery.After 72-h infusion,fasting serum insulin (Ins) and FFA in the blood were determined.The glucose infusion rat (GIR) was measured by hyperinsulinemia euglycemic clamp to evaluate the peripheral insulin resistance.The intravenous glucose tolerance test (ivgtt) and islet cell perifusion was conducted to evaluate the function of islet β-cell.The rats in two groups were sacrificed,and the pancreatic islets were isolated and collected.The levels of malondialdehyde (MDA) and reduced glutathione hormone (GSH) were detected in pancreatic tissues.The expressions of insulin receptor substrate-1 (IRS-1),insulin receptor substrate-2 (IRS-2),and glucose transporter-2 (Glut2)gene in islets were detected by real-time polymerase chain reaction (PCR).Results (1)The serum FFA concentration in the FFA group was higher than in NS group [(1.56 ± 0.21) mmol/L vs (0.65 ± 0.12)mmol/L,P ＜0.01].(2)The GIR was decreased significantly in FFA group compared with NS group(P ＜0.01).(3)The glucose that stimulated insulin secretion was decreased in the FFA group.(4)The levels of MDA were significantly higher in FFA group [(1.62 ± O.18) mmol/mg prot vs (0.76 ± 0.15) mmol/mg prot,P ＜0.01].The levels of GSH were lower in FFA group [(22.54 ±2.66) mg/g prot vs (36.58 ± 3.02) mg/g prot,P ＜ 0.01].(5) The gene cxprcssion of IRS-1 in islets was significantly decreased by [(36.8±1.8)％,P ＜0.01],and the expression of IRS-2 and Glut-2 was decreased by [(29.6±1.2) ％] and [(58.7 ± 2.1) ％] in FFA group,respectively(all P ＜0.01).Conclusions Lipid infusion in long time decreased the secretion of insulin and impaired the expression of insulin signal transduction molecules in islet βcells.