Perturbation of epithelial apicobasal polarity by rhomboid family-1 gene overexpression.

The human rhomboid family (RHBDF)1 gene is highly expressed in breast cancer under clinical conditions but not in normal mammary gland tissues. Silencing the RHBDF1 gene in breast cancer xenograft tumors leads to inhibition of tumor growth. We show in this study that artificially raising RHBDF1 protein levels in the mammary epithelial cells MCF-10A results in severe perturbations of the ability of the cells to form lumen-containing acini, either in 3-dimensional cell cultures or implanted in mouse mammary fat pads. Knocking down RHBDF1 with short hairpin (sh)RNA leads to restoration of acinus formation. Consistently, RHBDF1 overexpression gives rise to disordered distribution of polarity markers GM130 and laminin-5, which otherwise are located in apical and basal positions, respectively, in the acini. Further investigations reveal that RHBDF1 directly binds to Par6a, a component of a protein complex consisting of partitioning-defective scaffold protein (Par)6, Par3, renin-angiotensin system-related C3 botulinum toxin substrate (Rac)1, and cell-division cycle (Cdc)42, which is structurally critical to the formation of apicobasal polarity. RHBDF1 binding to Par6a results in collapse of the protein complex and thus disruption of polarity formation. Since early stages of breast cancer are characterized by the loss of mammary gland epithelial cell polarity, our findings indicate that perturbations of apicobasal polarity by high levels of RHBDF1 is a significant attribute in the development of breast neoplasia.-Peng, X.-M., Gao, S., Deng, H.-T., Cai, H.-X., Zhou, Z., Xiang, R., Zhang, Q.-Z., Li, L.-Y. Perturbation of epithelial apicobasal polarity by rhomboid family-1 gene overexpression.

Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice. Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

Efficacy of acupuncture for endometriosis-associated pain: a multicenter randomized single-blind placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain. DESIGN: A multicenter, randomized, single-blind, placebo-controlled trial. INSTITUTIONS: Four tertiary hospitals in Jiangxi and Hainan Provinces. SUBJECTS: Women with endometriosis-associated pain aged between 20 and 40 years. INTERVENTION: Subjects were assigned randomly to receive either acupuncture or sham acupuncture treatment for 12 weeks, starting one week before each expected menstruation and administered as a 30-minute session once per day, 3 times a week. During the menstruation period, acupuncture was administered daily when pelvic pain associated with endometriosis occurred. After acupuncture or sham acupuncture treatment, the subjects were followed for another 12 weeks. MAIN OUTCOME MEASURES: Changes in maximum pain as assessed with the visual analog scale (VAS) for various pelvic pain, duration of dysmenorrhea, and scores on the Multidimensional Pain Inventory, Beck Depression Inventory, Profile of Mood States, and Endometriosis Health Profile from baseline to week 12 and week 24. RESULTS: A total of 106 women were assigned randomly to the acupuncture and sham groups. In the acupuncture group, the reduction in the dysmenorrhea VAS score was significantly greater after treatment, but not at the end of the trial, compared to the sham group. The duration of pain was significantly shorter in the acupuncture group. All test scores were improved to a significantly greater extent in the acupuncture group than in the sham group at week 12 but not at week 24. Changes in nonmenstrual pelvic pain and dyspareunia VAS scores were not different between the groups. No severe adverse events or differences in adverse events were recorded. CONCLUSION: Acupuncture is an effective and safe method of relieving dysmenorrhea, shortening the pain duration, and improving wellbeing and quality of life in women with endometriosis-associated pain, although its efficacy fades after treatment is discontinued. CLINICAL TRIAL REGISTRATION NUMBER: NCT03125304.

[Status quo and factors influencing smoking cessation in cigarette smoking patients with coronary artery disease].

OBJECTIVE: To investigate the status quo of smoking cessation and analyze factors influencing smoking cessation in cigarette smoking patients with coronary artery disease (CAD). METHOD: A total of 350 smoking patients with CAD was surveyed by questionnaire, logistic regression analysis was performed to analyze factors influencing smoking cessation. RESULTS: Incidence of smoking cessation was 57.1% (200/350) in this cohort. Patients were divided into two groups, the elderly (> 65 years old, n = 111) and the young group (≤ 65 years old, n = 239). The smoking cessation rate in the elderly group is significantly higher than in the young group (71.2% vs. 50.6%, P < 0.001). Aged patients and patients with high cultural level are easier to give up smoking. Logistic analysis showed that age ≤ 65 years old (OR = 2.336, P = 0.004), low cultural level (OR = 1.310, P = 0.028), PCI (OR = 0.261, P < 0.001), coronary artery bypass graft (OR = 0.107, P = 0.004), total family income > 4000 RMB/month (OR = 1.828, P = 0.003) are risk factors for failed smoking cessation. There are 76 patients smoking again in current smokers, most due to lack of self-control (76.3%). Compared to the elderly group, there is a higher proportion of smoking again due to the need of daily communication and work in the young group. CONCLUSIONS: We still need to raise the awareness of smoking cessation for smoking patients with CAD. Following factors should be focused for tobacco control in CAD patients: younger age, lower cultural level, not treated with PCI or CABG, patients with smoking family members, higher body mass index and higher total family income.

CYP1B1-AS1 Is a Novel Biomarker in Glioblastoma by Comprehensive Analysis.

OBJECTIVE: Growing evidence shows that enhancer RNAs (eRNAs) are pivotal for tumor progression. In this research, our team aimed to identify the survival-related eRNAs and further explore their potential function in glioblastoma (GBM). METHODS: RNA-sequencing data in 31 tumor types were acquired from TCGA datasets. The survival-related eRNAs were identified by the use of Kaplan-Meier survival analyses and Spearman's correlation analyses. KEGG pathway enrichment analysis was completed to investigate the underlying signal paths of the critical eRNA. Pancancer assays were applied to explore the association between CYP1B1-AS1 and CYP1B1. RESULTS: We identified 74 survival-related eRNAs and focused on CYP1B1-AS1 which displayed the greatest cor value. CYP1B1 was identified as a regulatory target of CYP1B1-AS1. KEGG analyses suggested that CYP1B1-AS1 might play an essential role through CK-CKR mutual effect, complement and coagulation cascades, TNF signal path, and JAK-STAT signal path. The pancancer verification outcomes revealed that CYP1B1-AS1 was related to survival in 4 cancers, i.e., LIHC, KIRP, KICH, and KIRC. Association was discovered between CYP1B1-AS1 and the targeted gene, CYP1B1, in 29 cancer types. CONCLUSION: The outcomes herein provided the first evidence that overexpression of CYP1B1-AS1 might be a potential molecular biomarker for predicting the prognosis of patients with GBM.

[Clinical and prognostic features of the patients with esophageal squamous cell carcinomas as a first primary malignancy].

Objective: To retrospectively analyze the clinical characters and prognosis of the patients with Esophageal Squamous Cell Carcinomas as First Primary Malignancy (ESCCFPM), which will help us better understand the relationship between Esophageal Squamous Cell Carcinoma (ESCC) and other cancers, and to provide appropriate research evidence for the clinical diagnosis and treatment. Methods: The clinicopathological and follow-up data of 540 Patients with ESCCFPM between January 1, 2004 and December 31, 2016 were collected from the Surveillance, Epidemiology and End Results (SEER) database of National Cancer Institute. The Kaplan-Meier method was used to determine Overall Survival (OS) curves of ESCC patients, and the Log-Rank test was used to estimate differences in survival. The Cox proportional hazards models were adopted for the prognosis analyses. Results: Regarding the number of multiple primary malignancies (MPMs), 491 had two malignancies, 42 had three malignancies and 7 had four malignancies. ESCCFPM is more common among males. The high incidence age is between 61 and 80 years old. Tumors of the respiratory system (36.9%), were the most common MPMs followed by digestive system (35.2%) and reproductive system (8.9%). The 1-year, 3-year, 5-year OS rates for patients with ESCCFPM were 76.9%, 50.4% and 38.9%, respectively. The age of the ESCC diagnosed, T stage, time of occurrence, carcinoma number, lymph node dissection, surgery, radiotherapy and chemotherapy were the prognostic factor of overall survival for ESCCFPM patients. Age, race, T stage, time of occurrence surgery and radiotherapy were independent prognostic factors for the whole cohort by multivariate survival analysis. Conclusion: ESCCFPM,mainly two-lesion cancer, is most commonly found in respiratory system and digestive systems. Enhanced follow-up of respiratory and digestive tumors in ESCCFPM patients aged 61-80 may help identify multiple primary malignancies. Surgery, radiotherapy and chemotherapy may improve overall survival for ESCCFPM patients.

Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression.

BACKGROUND: Epidermal growth factor receptor (EGFR) signalling is critical in epithelial cancer development. Human rhomboid family-1 (RHBDF1) facilitates the secretion of TGFα, an EGFR ligand, in breast cancer; however, the underlying mechanism remains unclear. We evaluated the role for RHBDF1 in clathrin-coated vesicle (CCV)-dependent pro-TGFα membrane trafficking in breast cancer cells upon stimulation by G-protein coupled receptor (GPCR) agonists. METHODS: RHBDF1 was silenced in various breast cancer cells using shRNA. TGFα levels, subcellular localization, and secretion were evaluated using ELISA, immunofluorescent staining, and coimmunoprecipitation. Phosphorylation and expression of relevant proteins were measured by western blotting. RHBDF1-dependent cell viability and invasion were measured. FINDINGS: RHBDF1 mediates GPCR agonist-induced EGFR phosphorylation by promoting TGFα secretion in various types of breast cancer cells. RHBDF1 not only mediates ADAM17-dependent shedding of TGFα, but is essential in membrane trafficking of pro-TGFα. RHBDF1 silencing results in blocking of clathrin uncoating from CCV, a crucial step for the plasma membrane release of pro-TGFα. Interaction of RHBDF1 with auxilin-2, a CCV protein, determines the recruitment of HSC70 to CCV to facilitate clathrin uncoating. RHBDF1 function is required for the proliferation and mobility of breast cancer cells upon stimulation by Sphingosine 1 Phosphate (S1P), a GPCR agonist. We demonstrate a significant correlation between RHBDF1 overexpression and EGFR activation in breast cancer tissues. INTERPRETATION: RHBDF1 is an indispensable component of the protein trafficking machinery involved in GPCR-mediated EGFR transactivation, and is an attractive therapeutic target for cancer. FUND: National Natural Science Foundation of China (81,672,740 to ZSZ, 81,272,356 and 81,330,029 to LYL).

[Scanning electron microscopic observation of erythrocytes and endothelial cells of electrified death rabbits].

OBJECTIVE: To identify electrified death of animals without electric marks. METHODS: Two animal models (model A and model B) of electrified death without electric marks were established. Model A: right anterior limb and left hind limb of rabbits were soddened by 0.1 mol/L PBS, and two pieces of wet gause which were soaked in the 0.1 mol/L PBS were winded on the right anterior limb and left hind limb of them, respectively, and then two nake wires were winded outside of the gause; then, the two wires were connected to the alternating current of 220 voltage (A1 group) or 110 voltage (AZ group) electrified. Model B: two nake wires were fixed at the bilaterals of an oblong container, then a small quantities water were infunded into it, about 1.5 cm deep, and then, one rabbit was put in each time; finally, the two wires were connected to the alternating current of 220 voltage (B1 group) or 110 voltage (B2 group) electrified. The erythrocytes and endothelium of aorta and pulmonary artery of the animals were observed under scanning electron microscopes. RESULTS: Pores were found on the surface of the erythrocytes and endothelial cells of aorta and pulmonary artery of the electrified animals, which was absent in the control animals. The erythrocytes had the greatest perforated cell index among the three cells, followed by the pulmonary endothelium. CONCLUSION: The perforation phenomena can serve as an evidence of electrified death when no electric mark is observable.

Vascular endothelial growth factor suppresses TNFSF15 production in endothelial cells by stimulating miR-31 and miR-20a expression via activation of Akt and Erk signals.

Tumor necrosis factor superfamily-15 (TNFSF15; VEGI; TL1A) is a negative modulator of angiogenesis for blood vessel homeostasis and is produced by endothelial cells in a mature vasculature. It is known to be downregulated by vascular endothelial growth factor (VEGF), a major regulator of neovascularization but the mechanism of this interaction is unclear. Here we report that VEGF is able to stimulate the production of two microRNAs, miR-20a and miR-31, which directly target the 3'-UTR of TNFSF15. Additionally, we show that two VEGF-stimulated cell growth signals, Erk and Akt, are responsible for promoting the expression of miR-20a and miR-31. Treatment of human umbilical vein endothelial cells (HUVECs) with Akt inhibitor LY294002 results in diminished miR-20a and miR-31 production, while Erk inhibitor U0126 prevented VEGF-stimulated expression of miR-20a but not that of miR-31. Furthermore, inactivation of either Erk or Akt signals restores TNFSF15 gene expression. In an angiogenesis assay, elevated miR-20a or miR-31 levels in HUVECs leads to enhancement of capillary-like tubule formation in vitro, whereas lowered miR-20a and miR-31 levels results in an inhibition. These findings are consistent with the view that miR-20a and miR-31 mediate VEGF-induced downregulation of TNFSF15. Targeting these microRNA molecules may therefore provide an effective approach to inhibit angiogenesis.

[Observation the electroporation of blood cells in vitro by scanning electron microscope].

OBJECTIVE: To observe changes on cell membrane in blood cells after they were been electrified. METHODS: Blood were electrified for 5, 10, 20, 30 s, 1 min respectively, and Scanning electron microscope was used to detect the changes on their cell membranes. RESULTS: Pores were detected both on electrified erythrocytes and leukocytes with round or ellipse shapes. The erythrocytes often have one or more pores while the leukocytes often have more pores looked like cribble. The rates of perforated cells were increased with the prolonging time of electrification, 5 s with 6% and 1 min increased to 40%. CONCLUSIONS: Alternating current can cause the cell perforating, and the rates of perforated cell were increased with the prolonging time of electrification.

[Pharmacokinetics of a cisatracurium dose according to fat-free mass for anesthesia induction in morbidly obese patients].

OBJECTIVE: To compare the pharmacokinetics of cisatracurium between normal weight patients and morbidly obese patients. METHODS: Twelve obese ASA I-II patients (BMI≥35 kg/m2) undergoing laparoscopic Roux-en-Y gastric bypass and 12 normal weight ASA I-II patients (BMI of 18.5-24 kg/m2) undergoing laparoscopic surgery were enrolled. The obese patients were given a cisatracurium dose of 0.15 mg/kg according to the fat-free mass (FFM), and the non-obese patients received a dose of 0.15 mg/kg according to the total body weight. Plasma concentrations of cisatracurium was monitored in the patients with high-performance liquid chromatography (HPLC) before anesthetic induction and at 1, 2, 4, 6, 8, 10, 12, 15, and 20 min after cisatracurium administration and the pharmacokinetic parameters were computed. SBP, DBP, HR, MAP, SpO2 and PetCO2 were recorded before anesthetic induction (T0) and at 1 min (T1), 2 min (T2), 4 min (T3) after cisatracurium administration. RESULTS: Compared with those measured at T0, SBP, DBP and MAP in the 2 groups were significantly decreased at the time points of T1-3 (P<0.05). Compared with the non-obese patients, the obese patients showed significantly increased Hct level (P<0.05). The total clearance, apparent volume of distribution, and distribution and elimination half-life of the drug were similar between the 2 groups (P>0.05). The plasma concentration of cisatracurium at T1-2 was significantly decreased in the obese patients compared with that in the non-obese patients (P<0.05). CONCLUSION: Cisatracurium doses according to fat-free mass is clinically reasonable for inducing anesthesia in morbidly obese patients, but due to a prolonged muscle relax onset time, the timing of tracheal intubation should be delayed by 1-2 min.

[Protective effects of perfluorocarbon combined with ligustrazine against lung ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the effects of perfluorocarbon and ligustrazine in protecting the lungs against ischemia-reperfusion injury in rats. METHDS: Forty SD rats with ischemia-reperfusion lung injury were randomized equally into control, ligustrazine, perfluorocarbon, and perfluorocarbon plus ligustrazine groups and received the corresponding treatment via the tail vein 5 min before reperfusion. The lung tissues were harvested and the levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α) were detected 3 h after reperfusion. The pathological changes and pathological scores of the lung tissues were analyzed. RESULTS: MDA and MPO levels were significantly lower and SOD activities significantly higher in the lung tissues in the 3 treatment groups than in the control group (P<0.05). The rats in the combined treatment group showed a significantly lower MPO level and a significantly higher SOD activity than those treated with ligustrazine or perfluorocarbon alone (P<0.05). No significant difference was found in TNF-α levels in the lung tissues among the 4 groups (P>0.05). The lung tissues in the control group showed obvious edema and exudation, and the tissues in ligustrazine and perfluorocarbon groups showed no edema but with a few red blood cells and exudation; no edema was found in the combined treatment group with only a small amount of exudation. The pathological scores differed significantly among the 4 groups. CONCLUSION: Perfluorocarbon and ligustrazine, especially in combined use, can promote endogenous oxygen free radical scavenging, decrease peripheral blood proinflammatory cytokines, and inhibit neutrophils filtration in the lungs of rats with ischemia/reperfusion lung injury.

[Application of continuous epidural analgesia with ropivacaine and fentanyl during delivery].

OBJECTIVE: To evaluate the safety and efficiency of ropivacaine and fentanyl for continuous epidural analgesia during delivery. METHODS: Altogether 98 full-term primigravidas with vertex presentation were selected for this study. Epidural catheter was placed during delivery with the cervical dilation of 3 cm, and the mixture of 0.2% ropivacaine and 2 microgram/ml fentanyl at the initial dose of 5 ml was given for continuous epidural analgesia. Drug infusion was discontinued when the second stage of delivery started. Another 98 primigravidas of similar conditions without analgesia served as the control group. RESULTS: Analgesic group showed obvious pain-relieving effect (P<0.001) during the delivery, in which the active phase was significantly shortened (P<0.05). No obvious adverse effect arose in the mother and fetuses from the administration of analgesia. CONCLUSION: Continuous epidural analgesia by pumping ropivacaine and fentanyl is effective and convenient for pain relief during delivery, and can be beneficial to the smooth progress of delivery.

[Effect of hypervolemic hemodilution on C-reactive protein level in patients receiving spinal surgery].

OBJECTIVE: To investigate the changes in high-sensitivity C-reactive protein (hs-CRP) levels following acute hypervolemic hemodilution (AHH) in patients undergoing spinal surgery and assess the safety of AHH in terms of postoperative infection. METHODS: Forty patients undergoing spinal operation were randomly assigned into observation group and control group (n=20). Each patient was infused 4 ml/kg/h lactated Ringers solution for maintenance of the total blood volume, and in the observation group, the patients received additional infusion of 4% gelofusine solution at the rate of 20 ml/kg/h 30 min before the operation. Venous blood samples were collected to monitor the hematocrit (Hct), prothrombin time (PT), activated partial thromboplastin time (APTT) and hs-CRP before anesthesia (T0), 2 h after the beginning of the operation (T1), at the end of the operation (T2), and 24 h after the operation (T3). RESULTS: After AHH, Hct decreased significantly at T1 as compared with that at T0 (P<0.05) and that of the control group (P<0.01), but showed no significant difference between the two groups at T2. PT and APTT showed significant changes at T1 compared with T0 (P<0.05) but within the normal range, and were similar between the two groups at T3. hs-CRP increased significantly in the two groups at T3 compared with that at T0 (P<0.05), and a significant difference was noted between the two groups (P<0.01). CONCLUSION: AHH does not affect the hemodynamics and blood coagulation of the patients undergoing spinal surgery but causes a significant elevation of hs-CRP, suggesting an increased risk of postoperative infection.

[Inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine ameliorates hemodynamics and pulmonary histopathology in a porcine model of acute lung injury].

OBJECTIVE: To observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury. METHODS: Normal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations. RESULTS: The MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group. CONCLUSION: Combined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

[Stereological study of the placenta in parturients with different prophylactic measures for hypotension during spinal anesthesia for cesarean section].

OBJECTIVE: To explore the optimal approach to the prevention of hypotension during cesarean section for the benefits of both the parturients and the newborns. METHODS: Forty singleton full-term pregnant women undergoing elective cesarean delivery were randomly allocated into two equal groups. For prevention of hypotension during spinal anesthesia, ephedrine or pre-anesthetic volume with Voluven was administered. The changes of blood pressure, heart rate, and Apgar scores of the newborns were monitored and recorded, and the umbilical arterial blood gas variables were compared between the two groups. The placental samples were collected and immunohistochemistry for CD34 was performed for stereological study of the placental villous capillaries. RESULTS: The umbilical arterial PaCO(2), PaO(2) and Apgar scores showed no significant differences between the two groups (P<0.05). The heart rate, incidence of hypotension and the lactic acid value were significantly higher, and the umbilical arterial pH significantly lower in ephedrine group than in the Voluven group (P>0.05). While the length density of the villous capillaries was comparable between the two groups (P>0.05), the volume density of the villous capillaries was significantly decreased in ephedrine group (P<0.05). CONCLUSION: Pre-anesthetic volume expansion with Voluven can maintain stable hemodynamics during spinal anesthesia and also efficiently improve the tissue perfusion, microcirculation and uteroplacental blood flow, thus increasing the oxygen supply to the fetus.

Pretreatment with berberine and yohimbine protects against LPS-induced myocardial dysfunction via inhibition of cardiac I-[kappa]B[alpha] phosphorylation and apoptosis in mice.

Myocardial dysfunction is a common complication in sepsis and significantly contributes to the mortality of patients with septic shock. Our previous study demonstrated that pretreatment with berberine (Ber) protected against the lethality induced by LPS, which was enhanced by yohimbine, an [alpha]2-adrenergic receptor antagonist, and Ber combined with yohimbine also improved survival in mice subjected to cecal ligation and puncture. However, no studies have examined whether Ber and yohimbine reduce LPS-induced myocardial dysfunction. Here, we report that pretreatment with Ber, Ber combined with yohimbine, or yohimbine significantly reduced LPS-induced cardiac dysfunction in mice. LPS-provoked cardiac apoptosis, I-[kappa]B[alpha] phosphorylation, IL-1[beta], TNF-[alpha], and NO production were attenuated by pretreatment with Ber and/or yohimbine, whereas cardiac Toll-like receptor 4 mRNA expression, malondialdehyde content, and superoxide dismutase activity were not affected. These data demonstrate for the first time that pretreatment with Ber and/or yohimbine prevents LPS-induced myocardial dysfunction in mice through inhibiting myocardial apoptosis, cardiac I-[kappa]B[alpha] phosphorylation, and TNF-[alpha], IL-1[beta], and NO production, suggesting that activation of [alpha]2-adrenergic receptor in vivo may be responsible at least in part for LPS-induced cardiac dysfunction, and Ber in combination with yohimbine may be a potential agent for preventing cardiac dysfunction during sepsis.

[Postoperative analgesic effect of parecoxib sodium in patients with posterior spinal surgery].

OBJECTIVE: To investigate the postoperative analgesic effect of parecoxib sodium in patients with posterior spinal surgery. METHODS: Eighty patients undergoing posterior spinal surgery under general anesthesia were randomly divided into parecoxib sodium group and placebo group (n=40). All the patients received a single dose of m ml morphine (1.0 mg/ml) as the background analgesia immediately after the operation. The patients in parecoxib sodium group were given 40 mg parecoxib sodium intravenously, and those in the placebo group received an equivalent volume of saline instead, and at 24 and 48 h after the operation, the same dose was repeated. The visual analog pain score, patient satisfaction and adverse reactions were recorded after the administrations. RESULTS: Compared with the placebo group, the patients in parecoxib sodium group had significantly lowered VAS score at 6, 12, 24, and 48 h after the operation (P<0.05). No significant differences were noted in the patient satisfaction and adverse reactions between the two groups. CONCLUSION: Postoperative short-term use of parecoxib sodium can can provide good postoperative analgesic effect in patients undergoing posterior spinal surgery.