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To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-κB (HMGB1/NF-κB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. Methods Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-κB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). Results Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-κB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-κB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (μg/L): 60.1±8.7 vs. 80.5±9.1, NF-κB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. Conclusion IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-κB pathway.
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Objective To evaluate the clinical outcomes of severely resorbed edentulous mandibles with tilted implants and fixed prostheses. Methods Ten patients with severely resorbed edentulous mandibles were en-rolled. Each patient received 4 implants,two posteriors placed tilted implants. Immediate loading of tilted implants were applied in all cases using a fixed provisional prosthesis. All patients were finalized 3-4 months with fixed pros-theses. Results 40/40 implants with initial torque(>35N.cm)were followed 1-1.5 years presenting 100%surviv-al. Conclusion The method of using tilted implants and fixed prostheses in the cases of severely resorbed edentu-lous mandibles can achieve an ideal short-term and medium-term effects.
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Objective To explore the effects and related mechanism of Exendin-4 on secretion of extracellular matrix in high glucose-induced glomerular mesangial cells(GMCs). Methods GMCs were incubated in medium with glucose or Exendin-4 for the four groups: normal glucose group(NG group): cells were treated in medium with 5.6 mmol/L glucose; NG with Exendin-4 treatment group(NGE group): cells were treated with 5.6 mmol/L glucose and Exendin-4; high glucose group(HG group): cells were cultured with 30 mmol/L glucose; HG with Exendin-4 treatment group(HGE group): cells were treated with 30 mmol/L glucose and Exendin-4 at concentration of 3, 5, 10, 15, 30 nmol/L separately, which were cultured for 12, 24, 48 hours. GMCs treated with Exendin-4 were determined by assessing proliferation using a CCK8 method. The levels of fibronectin(FN), collagen type Ⅳ(Col-Ⅳ)in the cell supernatant were measured using enzyme-linked immunosorbent assay(ELISA). The gene levels of Col-Ⅳ, FN, and expression of inflammatory mediators including monocyte chemotactic protein 1(MCP-1), tumor necrosis factor-α(TNF-α), intercellular cell adhesion molecule-1(ICAM-1), transforming growth factor-β1(TGF-β1)were evaluated using reverse transcription PCR(RT-PCR); The expression of nuclear transcription factor-κB(NF-κB), glucagon-like peptide-l receptor(GLP-1R), and phosphorylation levels of mitogen-activated protein kinases(MAPKs)were evaluated by Western blot. Results(1)After treatment with 10 nmol/L Exendin-4 for 24 hour, the proliferation rate of GMCs was significantly decreased compared with 3 nmol/L, 5 nmol/L Exendin-4 treatment(P0.05). (2)The gene expression of FN, Col-Ⅳ and the inflammatory mediators, MCP-1, TNF-α, ICAM-1, TGF-β1 in HG group were significantly increased compared with the NG group,(all P<0.05). After treatment with Exendin-4, the levels of FN, Col-Ⅳ and the gene expression of TNF-α, MCP-1, ICAM-1, TGF-β1 were decreased(all P<0.05). (3)Compared with NG group, the expression of NF-κB and the phosphorylation of extracellular regulated protein kinases(p-Erk1/2), Jun N-terminal kinase(p-JNK)and, p38MAPK(p-p38MAPK)in the group of HG group were increased significantly, accompanied by the decrease of GLP-1R protein level(all P<0.05). Importantly, Exendin-4 treatment significantly reduced protein expression of p-Erk1/2, p-JNK, and NF-κB(all P<0.05), and the level of GLP-1R protein increased(P<0.05). Furthermore, specific Erk1/2, JNK or NF-κB inhibitors markedly blocked Exendin-4-mediated decrease in the levels of FN, Col-Ⅳ. Conclusion Exendin-4 treatment inhibits the secretion of extracellular matrix potentially through Erk1/2, JNK/NF-κB signaling in higher glucose induced GMCs.
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Objective To analyse the influencing factor,clinical appearance and solution of peri-implanti-tis,especially caused by cement remnant. Methods In this retrospective study 23 typical cases of peri-implantitis were collected in our implantology center from Jan.2016 to Dec.2016.The general data such as age,sex,systemic diseases,habits of smoking and alcohol,history of periodontitis,surgery process,materials and way of restoration were recorded in details.This study enrolled individuals from a private practice who had cement-retained implant res-torations,scheduled for regular implant maintenance or coming for consultation on a complication. Results All screw-retention(100%)and 50% cement retention peri-implantitis cases suffered from local and systemic diseases, 30% screw-retention and 20% cement retention healthy cases suffered from local and systemic diseases,which showed a significant differences(P<0.05),but there was no significant difference between screw and cement reten-tion in peri-implantitis group.85.7% of screw-retention and 50% of cement retention cases had a poor oral hygiene (PLI=2or3).Despite the other possible factors(such as diabetes,periodontitis and heavy smoker),8 cement-re-tained implants suffered from peri-implantitis.5 cases showed the cement remnant on the x-ray photo. Conclusion There are many pathogenic factors leading to peri-implantitis that may be single or combined.Cement remnant direct-ly leads to peri-implantitis.Clearance of excess cement together with scaling and laser treatment,or even combined with guided bone regeneration surgery are effective for treatment of peri-implantitis.
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Objective To study the sedative and analgesic effects of butorphanol combined with midazolam on critically ill patients treated by mechanical ventilation. Methods Fifty-eight patients who received mechanical ventilation, sedation and analgesia in intensive care unit (ICU) of Affiliated Huaian No.1 Hospital of Nanjing Medical University from January 2012 to December 2013 were enrolled. The patients were divided into a single midazolam group (30 cases) and a combination of butorphanol and midazolam group (combination with butorphanol group, 28 cases) according to the difference in types of sedative. The sedation for patients in the single midazolam group was induced firstly by intravenous injection of 0.05-0.10 mg/kg midazolam and followed by continuous infusion of the same drug 0.05 - 0.15 mg·kg-1·h-1 with a micro injection pump. The patients in the combination with butorphanol group were given a loading dose of butorphanol 10μg/kg and followed by continuous infusion of 10-20μg·kg-1·h-1 butorphanol combined with 0.05 - 0.15 mg·kg-1·h-1 midazolam by a micro pump. The Ramsay anesthesia score and visual analogue scale (VAS) were used to evaluate the sedative and analgesic effects. According to the Ramsay score, the sedation depths of patients in the two groups were maintained at 2-4 grades, and reassessed every 1-2 hours. The mean arterial pressure (MAP), heart rate (HR) and pulse blood oxygen saturation (SpO2) were observed before and after the drug administration in two groups. Results There were no statistically significant differences in MAP, HR and SpO2 between single midazolam group and combination with butorphanol group before treatment [MAP (mmHg, 1 mmHg=0.133 kPa): 121.3±6.2 vs. 118.6±8.7, HR (bpm):129.5±14.1 vs. 125.5±16.3, SpO2:0.744±0.112 vs. 0.756±0.131, all P>0.05]. Compared with those before treatment, after treatment, the above indexes in two groups were significantly improved, the differences being statistically significant [single midazolam group:MAP (mmHg) 88.7±6.5 vs. 121.3±6.2, HR (bpm) 85.3±13.4 vs. 129.5±14.1, SpO2 0.937±0.056 vs. 0.744±0.112; combination with butorphanol group: MAP (mmHg) 82.6±7.3 vs. 118.6±8.7, HR (bpm) 89.6±14.7 vs. 125.5±16.3, SpO2 0.943±0.078 vs. 0.756±0.131, all P < 0.05], and the degree of improvement of the combination with butorphanol group was better than that of the single midazolam group. The initial acting time of drugs and the time awakening from anesthesia in the combination with butorphanol group were shorter significantly than those in the single midazolam group (minutes: 33.6±6.2 vs. 73.3±12.2, 71.8±19.3 vs. 103.5±30.1, both P < 0.05), and the incidence of adverse reaction was lower obviously than that in the single midazolam group (0 vs.13.3%, P < 0.05). Furthermore, the score of VAS in the combination with butorphanol group was lower significantly than that in single midazolam group (8.4±1.2 vs. 2.4±0.8, P < 0.05). Conclusions Butorphanol combined with midazolam for treatment of critically ill patients with mechanical ventilation is a very effective sedative method, which may improve the degree of patients' tolerance towards the measure and reduce the incidence of adverse reactions.
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Objective To study PPARγ inhibitor(GW9662) ,on colon cancer SW480 cell proliferation and apoptosis intervened by Nimesulide(N) in vitro ,in order to investigate the role of PPARγpathway in colon cancer cell proliferation inhibition and apop‐tosis promotion induced by Nimesulide .Methods Cells were divided into 4 groups ,namely :the control group ,GW9662 group (GW9662 0 .1 ,0 .5 ,1 .0 ,5 .0μmol/L) ,N group ,GW9662+N group .MTT assay and FCM were used to determine proliferation ,ap‐optosis and cell cycle of SW480 cells .And the expression of PPARγ,p21Waf1 ,p27Kip1 ,Bcl‐2 ,Bax ,VEGF proteins were measured by Western‐blot .Results N inhibited SW480 cells proliferation in a time‐dependent manner (P0 .05) . Cell apoptosis rate of group N increased significantly ,compared with control group(P<0 .01) .The apoptosis rates of SW480 cells incubated with Nimesulide and GW9662 dropped significantly compared with Nimesulide alone (P<0 .01) .Above results showed that GW9662 could attenuate the effect of nimesulide on cell apoptosis and cell cycle .The results of Western‐blot :Compared with the control group ,the expression of PPARγ,p21Waf1 ,p27Kip1 ,Bax protein were up‐regulated significantly in nimesulide group(P<0 .05 or P<0 .01) ,but Bcl‐2 and VEGF were down‐regulated significantly(P<0 .01) .Compared with the nimesulide group ,the expres‐sion of PPARγ,p21Waf1 , p27Kip1 and Bax protein were down‐regulated obviously in GW9662+N group(P<0 .05 or P<0 .01) .Corre‐spondingly ,Bcl‐2 and VEGF were up‐regulated obviously(P<0 .05) .Conclusion N could effectively inhibit SW480 cell prolifera‐tion and induce its apoptosis .PPARγpathway may play an important role in proliferation inhibition and apoptosis induced by Nime‐sulide in colon cancer cell .
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BACKGROUND: It has been considered that Cestrum nocturnum L. (CNL) has the effects of antiarrhythmia, local anesthesia and central inhibition.OBJECTIVE: To investigate the analgesic effect of CNL extract on mice,so as to find new drugs for clinical treatment of pain.DESIGN: A randomized control observation.SETTING: Center of Modern Education and Department of Pharmacology,Gannan Medical College.MATERIALS: The experiments were carried out in the laboratory of scientific research center, Gannan Medical College between March and April in 2005. ① A total of 150 healthy adult Kunming mice were used in four independent experiments. ② Drugs: CNL extract was provided by the Department of Phytochemistry, Shenyang Pharmaceutical University (batch number: 2002080901), morphine hydrochloride injection by Shenyang No.1Pharmaceutical Factory (batch number: 000305), and naloxone hydrochloride injection by Yanqiao (Hunan) Pharmaceutical Co. Ltd., (batch number:20021109).METHODS: ① Effects of CNL extract on writhing times induced by acetic acid: Forty female mice were randomly divided into four groups with10 mice in each, and they were treated with intraperitoneal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 0.10 mg/g aminophenazone respectively. The intraperineal injection of 6 g/L glacial acetic acid was given after 15 minutes. The writhing times of mice within 15 minutes were observed and recorded in each group. ② Effects of CNL extract on the pain induced by hot pla in mice: Forty female mice were randomly divided into four groups with 10 mice in each, and they were treated with intraperineal injections of 0.02 mL/g saline, 0. 10 and 0.20 mg/g CNL extract and 0.10 mg/g morphine respectively. The pain responses were detected at 15, 30 and 60 minutes after administration. ③ The antagonistic effect of naloxone on morphine and CNL extract to the pain induced by hot plate in mice: Thirty female mice were randomly divided into three groups ith 10 mice in each group, and they were given intraperitoneal injections of 0.02 mL/g saline, naloxone 0.004 mg/g +morphine 0.01 mg/g and naloxone 0.004 mg/g+CNL extract 0.01 mg/g respectively. The pain responses were detected at 15, 30 and 60 minutes after administration respectively. ④ Effects of CNL extract on electrostimulation induced pain in mice: Forty mice were randomly divided into four groups with 10 mice in ach group, and they were administrated with intraperineal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 1 g/L morphine respectively. Repeated electrostimulations were given at 20, 35, 50 and 70minutes after administration, and the pain responses were detected by means of electrostimulation.MAIN OUTCOME MEASURES: ① Writhing times; ② Time for the pain response induced by hot plate; ③ Analgesic rate induced by electrostimulation.RESULTS: Totally 150 healthy adult Kunming mice were used in the four independent experiments, and all were involved in the analysis of results. ①Writhing times in the mice: 0.10 and 0.20 mg/g CNL extracts and 0.10 mg/g aminophenazone had very significant analgesic effects on writhing induced byacetic acid in mice, and the writhing times after administration were all fewer than those in the saline group (20.2±10.8, 14.5±7.6, 7.6±4.5,50.6±15.5, P ＜ 0.01), and the analgesic effects of CNL extract were dosedependently. ② Time for the pain response induced by hot plate: 0.10 and 0.20 mg/g CNL extracts had significant analgesic effects on the pain in duced by hot plate, and the time for pain sensation at 15, 30 and 60 minutes after administration were all longer than those in the saline group (P ＜ 0.05 or P ＜ 0.01), and the analgesic effect was dose-dependently. The times for pain sensation at each time point after administration in the naloxone 0.004 mg/g+CNL extract 0.01 mg/g group were all longer than those in the saline group, but those were close between the naloxone 0.004 mg/g+morphine 0.01 mg/g group and the saline group. ③ Analgesic rate induced by electrostimulation in the mice: The analgesic rates at20, 35, 50 and 70minutes after administration in the CNL extract 0.10 and 0.20 mg/g groups were all higher than those in the saline group (P ＜ 0.01).CONCLUSION: Our data suggested that CNL extract has obvious analgesic effect, and the analgesic intensity is dose-dependently. Naloxone, an opiate receptor antagonist, can antagonize the analgesic effect of morphine,but cannot antagonize that of CNL extract on mice with pain induced by hot plate, which indicates that CNL extract exert its analgesic role not through binding with opiate receptor.