Effect of intensive insulin therapy on high mobility group box-1/nuclear factor-κB pathway in severe traumatic brain injury patient with stress hyperglycemia / 中华危重病急救医学

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 Results Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the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.

ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic activity.

Our previous study suggests that heme oxygenase-1 (HO-1) may play an important role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in peritoneal metastasis of gastric cancer (PMGC) and explored the potential mechanism. We established animal model of PMGC by orthotopic implantation into nude mice of human gastric cancer cell line GC9811-P with high peritoneal metastasis potential. The mice were injected intraperitoneally with saline, CTX or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was determined by immunohistochemistry, and vascular endothelial growth factor (VEGF) level was determined by ELISA. We found that the number, volume, weight of peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg) group decreased remarkably compared with control group. MVD value and VEGF level of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased significantly, while the survival rate and survival time of the mice were higher than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species production and ERK phosphorylation in human umbilical vein endothelial cells. In conclusion, our results suggest that HO-1 plays an important role in PMGC and ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC.

An analysis of sedative and analgesic effects of butorphanol combined with midazolam on critically ill patients with mechanical ventilation / 中国中西医结合急救杂志

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.

The clinical application of early enteral nutrition in severe brain injury patients with mechanical ventilation / 肠外与肠内营养

Objective: To investigate the clinical effects of early enteral nutrition in severe brain injury patients requiring mechanical ventilation. Methods: 56 patients requiring mechanical ventilation were randomly divided into two groups:A(n=28),EEN group peptisorb,1 000 ml a day;B(n=28),control group,PN.The changes of serum total protein,blood albumin,immune globulin,lymphocyte count,nitrogen balance,oxgenation index(PaO2/FiO2),ventilation parameter and blood routine were measured.APACHE Ⅱ,incidence of ventilator-associated pneumoniasurvival rate for 28 days and days in hospital were observed.Results: Incidence of ventilator-associated pneumonia,28 d-survival rate and mean hospitalization day were significantly different(P