Effects of Preoperative High-Intensity Interval Training Combined With Team Empowerment Education in Lung Cancer Patients With Surgery: A Quasi-experimental Trial.

BACKGROUND: Cancer itself and surgery put a heavy burden on lung cancer patients, physiologically and psychologically. Enhancing self-efficacy during high-intensity interval training is essential for achieving the full benefit of pulmonary rehabilitation in lung cancer patients. OBJECTIVE: This study aimed to explore the effects of high-intensity interval training combined with team empowerment education on patients with lung resection. METHODS: This is a quasi-experimental trial with a pretest-posttest design. Participants were assigned to one of the 3 groups according to the order of admission: (1) combined intervention group, (2) intervention group, or (3) routine care group. The outcome measures included dyspnea, exercise capacity, exercise self-efficacy, anxiety, depression, postoperative indwelling time of thoracic drainage tube, and total in-hospital stay. RESULTS: Per-protocol results showed that dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression of the patients in the combined intervention group were significantly improved. However, no significant difference was observed in postoperative indwelling time of thoracic drainage tube or total in-hospital stay among the 3 groups. CONCLUSION: This hospital-based short-term high-intensity interval training combined with team empowerment education for lung cancer patients undergoing surgery was safe and feasible, indicating this program can be a promising strategy to manage perioperative symptoms. IMPLICATIONS FOR PRACTICE: This study provides evidence supporting preoperative high-intensity interval training as a promising method to make the best use of preoperative time, thus improving adverse symptoms in lung cancer patients undergoing surgery, and also provides a new strategy to raise exercise self-efficacy and promote patients' rehabilitation.

Effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Clinical Indicators of Effects of Yoga Breathing Exercises on Patients With Lung Cancer After Surgical Resection: A Randomized Controlled Trial.

BACKGROUND: Cancer itself and surgery pose a heavy burden on adults with lung cancer. Yoga breathing exercises have been proposed as a form of pulmonary rehabilitation exercises to improve these patients' perioperative outcomes. OBJECTIVE: To investigate the impact of yoga breathing exercises based on a problem-solving model on dyspnea, exercise capacity, anxiety, depression, and postoperative indwelling time of thoracic drainage tube and compliance in adults with lung cancer undergoing surgery. METHODS: One hundred eight lung cancer patients were randomly assigned to receive problem-solving model-based yoga breathing exercises, yoga breathing exercises, or usual care. Outcomes were collected at admission, the day before surgery, and at discharge. RESULTS: Patients in the combined intervention group showed a significantly greater improvement in dyspnea, exercise capacity, and anxiety compared with the control group. Yoga breathing training can significantly improve patients' dyspnea and anxiety. Significant difference favoring the combined group was observed in exercise capability and compliance between the 2 intervention groups. However, there was no significant difference in depression or indwelling time of thoracic drainage tube among the 3 groups at any time point. CONCLUSION: Findings indicate that yoga breathing exercises are effective in alleviating perioperative symptoms of lung resection patients. Compared with yoga breathing exercises, applying additional problem-solving model may achieve a better effect. IMPLICATIONS FOR PRACTICE: Yoga breathing exercises can be considered as a promising pulmonary rehabilitation strategy for lung cancer patients with surgery. The problem-solving model could be integrated into yoga breathing exercises in clinical practice to enhance the rehabilitation effect.

Effects of home-based telehealth on the physical condition and psychological status of patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIMS: This systematic review and meta-analysis aimed to evaluate the effects of home-based telehealth compared with usual care on six-minute walking distance (6MWD), health-related quality of life, anxiety and depression in patients with chronic obstructive pulmonary disease. METHODS: We identified randomized controlled trials through a systematic multidatabase search. Titles and abstracts were assessed for relevance. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta-analyses were conducted using Review Manager and Stata. RESULTS: We included 32 randomized controlled trials (n = 5232). Devices used for home-based telehealth interventions included telephones, videos, and combined devices. The quality of the evidence was downgraded due to high risk of bias, imprecision, and inconsistency. Home-based telehealth significantly increased 6MWD by 35 m (SD = 30.42) and reduced symptom burden by 3 points (SD = -2.30) on the COPD assessment test compared with usual care. However, no significant differences in anxiety and depression were noted between the home-based telehealth group and the standard care group. In subgroup analysis, home-based telehealth significantly improved 6MWD and health status after 6-12 months and >12 months. CONCLUSION: Low quality evidence showed that home-based telehealth interventions reduce symptom burden and increase walking distance to a clinically meaningful extent in patients with COPD. However, no effects on depression and anxiety were observed.

Auricular Acupressure for Improving Sleep Quality in Patients With Lung Cancer: A Systematic Review and Meta-analysis.

This meta-analysis was conducted to systematically evaluate the efficacy and safety of auricular acupressure on sleep quality in patients with lung cancer. Nine articles with a total of 802 patients were retrieved after searching on 11 electronic databases. Results of the meta-analysis showed that auricular acupressure improved sleep score (standard mean difference: -0.80, 95% confidence intervals: -1.30 to -0.30, P = .002) and reduced sleep disturbance rate (risk ratio: 0.65, 95% confidence intervals: 0.51-0.84, P = .001) and sleep medicine usage (risk ratio: 0.26, 95% confidence intervals: 0.11-0.65, P = .004) significantly. Our review suggests that auricular acupressure is effective and relatively safe in improving sleep quality among patients with lung cancer.

Active Cycle of Breathing Technique: A Respiratory Modality to Improve Perioperative Outcomes in Patients With Lung Cancer.

BACKGROUND: Cancer and surgery put a physiologic and psychological burden on patients with lung cancer. The active cycle of breathing technique (ACBT) has been considered as an effective airway clearance method for patients with lung diseases. Its effectiveness on perioperative outcomes in patients with lung cancer warrants study. OBJECTIVES: This prospective study explored the effects of the ACBT on patients with lung cancer undergoing surgical resection. METHODS: Patients were randomly allocated to the intervention (N = 34) or control group (N = 34). The intervention group received the ACBT, and the control group received usual pre-/postoperative breathing exercises. Outcomes included dyspnea, exercise capacity, anxiety, depression, and postoperative pulmonary complications. Intention-to-treat analysis was also performed. FINDINGS: Dyspnea, anxiety, depression, and postoperative pulmonary complications were significantly improved at discharge for patients in the intervention group.

The Protective Effect and Mechanism of Dexmedetomidine on Diabetic Peripheral Neuropathy in Rats.

OBJECTIVE: To investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage. METHODS: Eighty male Sprague-Dawley (SD) rats were randomly allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine treated group (YOH group). DPN was induced by intraperitoneal administration of streptozocin (STZ) (35 mg/kg). The body weights, blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the motor, and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured. Then the sciatic nerve was isolated for H&E staining and immunohistochemical staining. The oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD), and glutathione peroxidase (GSH-Px) and apoptosis related cytokines such as Bax, Bcl-2, and caspase-3 were estimated. RESULTS: There was no significant difference of the blood glucose and body weight among the DPN group, DEX group, and YOH group. H&E staining showed that DEX treatment can ameliorate the damage of sciatic nerve cells. In the DPN group, MWT, TWL, MNCV, and SNCV were significantly reduced compared with the C group (P < 0.05). In DEX group rats, MWT, TWL, MNCV, and SNCV were increased significantly (P < 0.05) compared with the DPN group and YOH group rats. Lower SOD and GSH-Px, and higher MDA were found in the DPN group compared with the C group (P < 0.01), and DEX treatment restored SOD, GSH-px, and MDA activity significantly (P < 0.01). The expression levels of Bax and caspase-3 were increased, while that of Bcl-2 was decreased significantly in the DPN group compared with the C group (P < 0.05). In the DEX group, the expression levels of Bax and caspase-3 were decreased significantly (P < 0.05), while that of Bcl-2 was increased significantly (P < 0.05) compared with the DPN group and the YOH group. CONCLUSION: The results of this study demonstrated that DEX has the inhibitory and protective effects on DPN of rats. This may be associated with its antioxidative and anti-apoptosis responses.

[Analysis of the Related Risk Factors of Cerebral AVM Hemorrhage and the Relationship Between EPCs and SDF-1 in Brain AVM].

OBJECTIVE: To explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages. METHODS: A retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed. RESULTS: The size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages ( P<0.05). There was no significant difference in EPCs between cerebral hemorrhage group and non-hemorrhage group ( P>0.05). CONCLUSION: Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM.

Optimal Dexmedetomidine Dose to Prevent Emergence Agitation Under Sevoflurane and Remifentanil Anesthesia During Pediatric Tonsillectomy and Adenoidectomy.

Background: Emergence agitation (EA) is a common pediatric complication after sevoflurane anesthesia that can be prevented with dexmedetomidine. However, an inappropriate dose of dexmedetomidine can cause prolonged sedation and cardiovascular complications. Thus, we evaluated the optimal dose (ED95) of dexmedetomidine for preventing EA with sevoflurane and remifentanil anesthesia after pediatric tonsillectomy and adenoidectomy. Methods: We enrolled American Society of Anesthesiologists (ASA) I and II children 3-7 years of age who underwent tonsillectomy with adenoidectomy. During induction, dexmedetomidine was infused for 10 min. Anesthesia was induced with sevoflurane and maintained with sevoflurane and remifentanil, resulting in a bispectral spectrum index (BIS) range from 40 to 60. Extubation time, surgical and anesthetic duration time, and duration time in the postanesthesia care unit (PACU) stay were recorded. EA [measured with Pediatric Anaesthesia Emergence Delirium (PAED) scores] and pain [measured with Face, Legs, Activity, Cry, Consolability (FLACC) scores] were assessed at extubation (E0), 15 min after extubation (E1), and 30 min after extubation (E2). If EA occurred, the next surgical procedure included increased dexmedetomidine by 0.1 µg/kg, and if not, the drug was reduced by 0.1 µg/kg. Results: The 50% effective dose (ED50) of dexmedetomidine for preventing EA after sevoflurane and remifentanil anesthesia for tonsillectomy and adenoidectomy was 0.13 µg/kg, and its 95% confidence interval is 0.09-0.19 µg/kg; ED95 was 0.30 µg/kg, and its 95% confidence interval is 0.21-1.00 µg/kg. Conclusion: Intravenous dexmedetomidine infusion at ED50 (0.13 µg/kg) or ED95 (0.30 µg/kg) during induction for 10 min can prevent half or almost all EA after sevoflurane and remifentanil anesthesia during pediatric tonsillectomy and adenoidectomy.

Adrenomedullin Reduces Secondary Injury and Improves Outcome in Rats with Fluid Percussion Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a devastating neurologic injury and remains a major cause of death in the world. Secondary injury after TBI is associated with long-term disability in patients with TBI. This study evaluated adrenomedullin (AM) on secondary injury and neurologic functional outcome in rats after TBI. METHODS: Forty-eight Sprague Dawley rats were randomly assigned into 3 groups: sham, TBI, and TBI with AM groups. TBI was induced by fluid percussion injury, and AM was intravenously injected. Neurologic function was examined at 2, 3, and 7 days after TBI. Enzyme-linked immunosorbent assay was used to test tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-8 levels in the brain. Brain edema and blood-brain barrier (BBB) permeability in brain tissue were tested. Western blot was used to examine the expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase-3. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to test the apoptosis. RESULTS: Compared with the sham group, TNF-α, IL-1ß, and IL-6 levels, brain edema, BBB permeability, neurologic examination scores, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, and expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase-3 significantly increased in the TBI group. AM treatment significantly inhibited TBI-induced effects. CONCLUSIONS: AM can improve neurologic function and ameliorate brain injury in rats with TBI. AM exerts its neuroprotective effect via its anti-inflammatory and antiapoptotic effect.

Low dose of dexmedetomidine as an adjuvant to bupivacaine in cesarean surgery provides better intraoperative somato-visceral sensory block characteristics and postoperative analgesia.

OBJECT: In this study, we aimed to investigate the beneficial effects of dexmedetomidine on somato-visceral sensory block characteristcs, postoperative analgesia and stress response of intrathecal bupivacaine administration in women undergoing cesarean section, and to find out which dose is better. METHODS: Sixty parturients with the American Society of Anesthesiologists (ASA) physical status I or II were anesthetized with intrathecal bupivacaine(10mg) alone or in combination with dexmedetomidine (3 µg and 5 µg) to undergo cesarean section. The anesthetic parameters, postoperative analgesia and stress responses were monitored. RESULTS: Co-administration of dexmedetomidine(3 µg and 5 µg) prolonged the duration of motor and sensory block compared with bupivacaine(10mg) alone. Less supplemental dose of lidocaine and fentanyl were required in dexmedetomidine(3 µg and 5 µg) co-administration groups. Visceral traction response and abdominal muscle relaxation in operation were better in dexmedetomidine(3 µg and 5 µg) co-administration groups. No difference in haemodynamics was detected among groups. There was no significant difference in Apgar scores, neonatal umbilical pH, oxygen pressure, carbon dioxide pressure and lactate level among groups. Postoperative plasma IL-6 and cortisol levels were lower in dexmedetomidine(3 µg and 5 µg) co-administration groups. At 6 hour after operation the visual analogue scale (VAS) was smaller in dexmedetomidine(3 µg and 5 µg) co-administration groups. The uterine contraction pain at 6 and 12 hour after operation and supplemental analgesics had no difference across three groups. No difference of side effects(shivering, nausea and vomiting, itching), the first anal aerofluxus time and intraoperation tramadol dose were detected among the three groups. CONCLUSION: The use of dexmedetomidine especially at the dose of 3µg as an adjuvant to bupivacaine in cesarean surgery provides better intraoperative somato-visceral sensory block characteristcs and postoperative analgesia, which produced no influence on Apgar scores, side effects and stress response.

Protective effects of propofol against whole cerebral ischemia/reperfusion injury in rats through the inhibition of the apoptosis-inducing factor pathway.

Cerebral ischemia/reperfusion (I/R) injury could cause neural apoptosis that involved the signaling cascades. Cytochrome c release from the mitochondria and the followed activation of caspase 9 and caspase 3 are the important steps. Now, a new mitochondrial protein, apoptosis-inducing factor (AIF), has been shown to have relationship with the caspase-independent apoptotic pathway. In this study, we investigated the protective effects of propofol through inhibiting AIF-mediated apoptosis induced by whole cerebral I/R injury in rats. 120 Wistar rats that obtained the permission of the animal care committee of Harbin Medical University were randomly divided into three groups: sham group (S group), cerebral ischemia/reperfusion injury group (I/R group), and propofol treatment group (P group). Propofol (1.0mg/kg/min) was administered intravenously for 1h before the induction of ischemia in P group. The apoptotic rate in three groups was detected by flow cytometry after 24h of reperfusion. The mitochondrial membrane potential (MMP) changes were detected via microplate reader. The expressions of B-cell leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and AIF were evaluated using Western blot after 6h, 24h and 48h of reperfusion. The results of our study showed that apoptotic level was lower in P group compared with I/R group and propofol could protect MMP. The ratio of Bcl-2/Bax was significantly higher in P group compared with I/R group. The translocation of AIF from mitochondrial to nucleus was lower in P group than that in I/R group. Our findings suggested that the protective effects of propofol on cerebral I/R injury might be associated with inhibiting translocation of AIF from mitochondrial to the nucleus in hippocampal neurons.

The inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons.

Excessive K(+) efflux via activated voltage-gated K(+) channels can deplete intracellular K(+) and lead to long-lasting membrane depolarization which will promote neuronal apoptosis during ischemia/hypoxia injury. The Kv2.1 potassium channel was the major component of delayed rectifier potassium current (Ik) in pyramidal neurons in cortex and hippocampus. The neuronal protective effect of propofol has been proved. Delayed rectifier potassium current (Ik) has been shown to have close relationship with neuronal damage. The study was designed to test the inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons. Whole-cell patch clamp recordings and Western blot analysis were used to investigate the electrophysiological function and protein expression of Kv2.1 in rat parietal cortical neurons after propofol treatment. We found that propofol concentration-dependently inhibited Ik in pyramidal neurons. Propofol also caused a downward shift of the I-V curve of Ik at 30µM concentration. Propofol significantly inhibited the expression of Kv2.1 protein level at 30µM, 50µM, 100µM concentration. In conclusion, our data showed that propofol could inhibit Ik, probably via depressing the expression of Kv2.1 protein in rat cerebral parietal cortical neurons.

Effects of propofol and sevoflurane on aquaporin-4 and aquaporin-9 expression in patients performed gliomas resection.

Post-operative cerebral edema is a threat for patients performed gliomas resection. Some studies have shown that general anesthesia drugs, such as, propofol had neuroprotective effect. Aquaporin-4 (AQP4) and Aquaporin-9 (AQP9) play an important role in maintaining brain water homeostasis under various conditions. The aim of this study was to compare the effect of propofol or sevoflurane on expression of AQP4 and AQP9 in patients performed gliomas resection. 30 patients performed gliomas resection were included in this study. The patients were randomly divided into two groups: propofol group and sevoflurane group. Fresh human gliomas specimens were obtained and hematoxylin eosin (HE) staining, immunohistochemical staining and Western blot analysis were used for observation of the expression of AQP4 and AQP9. The immunohistochemical staining of the sections showed that the percentage of AQP4 positive cells in the propofol group (14.3±4.61%) was significantly lower than that in sevoflurane group (37.3±10.01%) (n=15, P<0.05). There was no significant difference in the percentage of AQP9 positive cells in propofol group and sevoflurane group (25.8±2.67 versus 28.1±7.81%, n=15, P>0.05). Western blot analysis confirmed the immunohistochemistry results. AQP4 protein level in propofol group was significantly lower than that in sevoflurane group (1.4±0.13 versus 1.7±0.12, P<0.05). Western blot analysis did not show any difference of expression of AQP9 protein between the propofol group and sevoflurane group (2.0±0.13 versus 2.1±0.13, P>0.05, n=6). AQP4 expression was lower in patients of propofol group than that in sevoflurane group. Our results suggested that propofol could inhibit the expression of AQP4.

Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in Han nationality nephrectomy patients.

OBJECTIVE: Tramadol is a synthetic opioid which has analgesic efficacy in the postoperative pain. It is metabolized by polymorphic enzyme cytochrome P450 (CYP2D6). Patients with different CYP2D6 genotypes would have different responses to tramadol in pain relief. The CYP2D6*10 allele is the most common allele in a Chinese population. The aim of this study was to evaluate whether the different CYP2D6*10 genotypes have an effect on the postoperative tramadol analgesia in the Chinese population after elective nephrectomy. METHODS: One hundred and twenty patients after performed elective nephrectomy were enrolled in this study after being approved by the local Ethics Committee. The patients were given patient-controlled analgesia (PCA) which included 10 mg/ml tramadol after receiving a loading dose of 100 mg tramadol and 1 mg granisetron intravenously. Blood samples were collected after induction of anesthesia. The CYP2D6*10 polymorphism was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). According to the results, the patients were divided into three groups (CYP2D6*1/*1, n = 33; CYP2D6*1/*10, n = 28; CYP2D6*10/*10, n = 50). The total consumption of tramadol, visual analogue scale (VAS) score, and PCA control times among the three genotype groups for 2, 4, 24, 48, and 72 h after operation were compared. RESULTS: Nine out of 120 patients were dropped out of the study; 111 patients completed the study. The frequency of CYP2D6*10 allele was 57.7%. The demographic data among the three groups were comparable. The consumption of tramadol, patient self-control times of pump, and VAS score in CYP2D6*10/*10 group were significantly higher than that in CYP2D6*1/*1 or CYP2D6*1/*10 group at 2 and 4 h (P < 0.05), while it did not differ between CYP2D6*1/*1 and CYP2D6*1/*10 group (P > 0.05). There was no difference in the incidence of nausea and vomiting among the three groups (P > 0.05). No sever apnea was recorded in these groups. CONCLUSIONS: Different CYP2D6*10 genotypes have an influence on the analgesic effect of tramadol in Han nationality patients after elective nephrectomy.

Propofol prevents neuronal mtDNA deletion and cerebral damage due to ischemia/reperfusion injury in rats.

Propofol is a commonly used intravenous anesthetic that has been demonstrated to be neuroprotective against cerebral ischemia-reperfusion (I/R) injury. It remains unclear whether this protective effect has any relationship with the prevention of neuronal mitochondrial deoxyribonucleic acid (mtDNA) deletion. In this study, 81 Wistar rats were randomly divided into three groups (n = 27 each): sham (S group), ischemia/reperfusion (I/R group), or propofol (P group). Cerebral ischemia was induced by clamping the bilateral common carotid arteries for 10 min. A polymerase chain reaction (PCR) was conducted to determine mtDNA deletion. The mitochondrial membrane potential (MMP) changes were detected via microplate reader. The neuronal ultrastructure was visualized via electron microscope. MMP significantly decreased after I/R (P<0.05 compared with the S group). Severe damage to the ultrastructure of neuronal mitochondria was observed in cerebral I/R injury. When propofol (1.0mg/kg/min) was administered intravenously for 1h prior to the induction of I/R, the neuronal structure and MMP were well preserved, and mtDNA deletion was reduced after ischemia/reperfusion injury compared with the I/R group (P<0.05). These data suggested that propofol prevented mtDNA deletion and preserved a normal structure and MMP, which are important for normal mitochondrial function and increase neuronal resistance to I/R injury.

Inhibition of LN-308 glioma cell proliferation and migration by retinoic acid amide through activation of Akt pathway.

The present study was performed to investigate the effect of retinoic acid amide (RAA) on the expression of integrin α3ß1, rate of cell proliferation and migration in p53-deficient glioma cell line, LN-308. The results revealed promotion of integrin α3 expression, reduction in proliferation and migration in RAA treated cells compared to the control LN-308 glioma cells. Promotion of RAA induced integrin α3ß1 expression led to the enhancement in cyclin-dependent kinase nuclear localization and activation of Akt pathway. In addition, RAA treatment inhibited the expression of nuclear factor-κB, Bcl-2 and epidermal growth factor receptor (EGFR). These factors are responsible for promoting the rate of cell proliferation and survival in the carcinoma cells. Thus RAA treatment inhibits rate of LN-308 glioma cell proliferation and migration through increase in integrin α3ß1 expression and activation of Akt pathway. Therefore, RAA can be of therapeutic importance for the treatment of glioma.

N-heterocyclic carbene catalyzed cyclocondensation of α,ß-unsaturated carboxylic acids: enantioselective synthesis of pyrrolidinone and dihydropyridinone derivatives.

The catalytic cyclocondensation of in situ activated α,ß-unsaturated carboxylic acids was developed. N-heterocyclic carbenes efficiently catalyzed the generation of α,ß-unsaturated acyl azolium intermediates from α,ß-unsaturated carboxylic acids via in situ generated mixed anhydrides for the enantioselective [3+2] and [3+3] cyclocondensation with α-amino ketones and alkyl(aryl)imines, respectively. The corresponding pyrrolidinones and dihydropyridinones were isolated in good yields with high to excellent enantioselectivities.

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury.

Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH2O for 4 h and randomly given FiCO2 to achieve normocapnia (PaCO2 at 35-45 mm Hg) or hypercapnia (PaCO2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH2O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways.

Diabetic neuropathic pain development in type 2 diabetic mouse model and the prophylactic and therapeutic effects of coenzyme Q10.

UNLABELLED: The early onset of type 2 diabetes mellitus (DM), driven by increasing obesity, is associated with peripheral neuropathy. Here, we characterize diabetic neuropathic pain in New Zealand obese diabetic mice (NZO/HILtJ) as a polygenic model of obesity with type 2 diabetes and investigate the role of coenzyme Q10 (CoQ10) in the prevention and treatment of diabetic neuropathic pain. Since the overexpression of mitogen-activated protein kinase (MAPK), nuclear factor-κB proteins (NF-Kb), toll-like receptor 4 (TLR4) and downstream cytokines (such as CCL2, CXCL10) are considered important factors contributing to the development of neuropathic pain, the expression of these factors and the inhibitory effects of CoQ10 were evaluated. NZO/HILtJ mice spontaneously developed type 2 DM and increased body mass with diabetic neuropathic pain. CoQ10 treatment decreased pain hypersensitivity and long-term supplementation prevented the development of diabetic neuropathic pain but did not attenuate diabetes. Spinal cord, blood serum, liver tissue, and dorsal root ganglia (DRG) from diabetic mice demonstrated increased lipid peroxidation, which was decreased by CoQ10 treatment. The percentage of positive neurons of p65 (the activated marker of NF-KB) and MAPK in DRG were significantly higher in DM mice compared to controls. However, CoQ10 treatment significantly decreased p65 and MAPK positive neurons in the DRG of DM mice. RT-PCR demonstrated that elevated levels of mRNA of CCL2, CXCL10 or TLR4 in the spinal cord of DM mice decreased significantly when DM mice were treated with CoQ10. CONCLUSION: This model may be useful in understanding the mechanisms of neuropathic pain in type 2 DM induced neuropathic pain and may facilitate preclinical testing of therapies. CoQ10 may decrease oxidative stress in the central and peripheral nervous system by acting as an anti-oxidant and free-radical scavenger. These results suggest that CoQ10 might be a reasonable preventative strategy for long-term use and using CoQ10 treatment may be a safe and effective long-term approach in the treatment of diabetic neuropathy.