Fascia iliaca compartment block mitigates the fluctuations in heart rate variability and reduces pain with opioid consumption in elderly individuals with hip fractures: A randomized controlled trial.

Background: Hip fractures, commonly known as the "terminal fracture of life," frequently necessitate prompt surgical intervention and are accompanied by significant perioperative pain. Objective: This investigation was performed to assess the impact of fascia iliaca compartment block (FICB) on heart rate variability during the perioperative period in elderly individuals with hip fractures. Design: Single-center, randomized, controlled clinical trial. Setting: The study was conducted from September 2021 to February 2023 at one tertiary care hospital in China. Participants: Patients aged ≥60 years who underwent general anesthesia for hip fracture surgery were screened for enrollment. Eighty patients were initially assessed for eligibility, 70 underwent randomization, and 62 were included in the final analysis. Methods: Preoperatively, the patients were randomly allocated to either receive (Group F) or not receive (Group C) ultrasound-guided suprainguinal FICB. The primary endpoint was heart rate variability indicators at the corresponding time points. The secondary endpoints included the mean arterial pressure and heart rate measured at different time points [upon admission to the operating room (T1), during positioning (T2), at the time of skin incision (T3), 30 min after the start of surgery (T4), and 6 h postoperatively (T5)] and visual analogue scale (VAS) score, dose of oral pain medication over 24 h, and satisfaction scores were valued. Results: Compared with Group C, Group F had a significantly reduced low-frequency band, high-frequency band, and low-/high-frequency band ratio at T3, T4, and T5 (P < 0.05). Group F also had a lower heart rate at T2, T3, T4, and T5 (P < 0.05). Moreover, Group F had lower flurbiprofen dosages at 24 h postoperatively (P < 0.05) and lower resting VAS scores at 6 and 24 h postoperatively (P < 0.05). Conclusion: Utilization of ultrasound-guided FICB has the potential to yield efficacious analgesic effects, mitigate the pronounced fluctuations in heart rate induced by surgical stimulation, and maintain autonomic function stability to a certain degree.

Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke.

Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-ß/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-ß/T cells.

Molecular Hydrogen Mediates Neurorestorative Effects After Stroke in Diabetic Rats: the TLR4/NF-κB Inflammatory Pathway.

Diabetes is an independent risk factor for stroke and amplifies inflammation. Diabetic stroke is associated with a higher risk of death and worse neural function. The identification of effective anti-inflammatory molecules with translational advantages is particularly important to promote perioperative neurorestorative effects. Applying molecular hydrogen, we measured blood glucose levels before and after middle cerebral artery occlusion (MCAO), 48-h cerebral oedema and infarct volumes, as well as 28-day weight, survival and neurological function. We also measured the levels of TLR4, NF-κB p65, phosphorylated NF-κB p65, catecholamines, acetylcholine and inflammatory factors. All measurements comprehensively showed the positive effect and translational advantage of molecular hydrogen on diabetic stroke. Molecular hydrogen improved the weight, survival and long-term neurological function of rats with diabetic stroke and alleviated changes in blood glucose levels before and after middle cerebral artery occlusion (MCAO), but no difference in circadian rhythm was observed. Molecular hydrogen inhibited the phosphorylation of NF-κB and significantly reduced inflammation. Molecular hydrogen mediates neurorestorative effects after stroke in diabetic rats. The effect is independent of circadian rhythms, indicating translational advantages. The molecular mechanism is related to the TLR4/NF-κB pathway and inflammation. Molecular hydrogen (H2) affects outcomes of ischemic stroke with diabetes mellitus (DM).

Anaesthesia provision, infrastructure and resources in the Heilongjiang Province, China: a cross-sectional observational study.

OBJECTIVE: The aim of this study was to explore the current status of the anaesthesia provision, infrastructure and resources in the Heilongjiang Province, China. DESIGN: A cross-sectional observational study of hospitals, anaesthesiologists, assistant anaesthesiologists and anaesthetic nurses in the Heilongjiang Province. SETTING: All hospitals in the Heilongjiang Province. PARTICIPANTS: The hospitals, anaesthesiologists (attending physicians, associate chief physicians and chief physicians), assistant anaesthesiologists (licenced assistant physicians, resident physicians and other trainees) and anaesthetic nurses. MAIN OUTCOME MEASURES: Standard descriptive statistics (percentages and numbers) were used to summarise the data. RESULTS: The investigation involved 1123 hospitals, 405 of these hospitals had anaesthesiology departments (36.06%). There were 2406 anaesthesiologists, 175 assistant anaesthesiologists and 409 anaesthetic nurses. The proportion of anaesthesiologists was 56.60% in tertiary hospitals, 40.15% in secondary hospitals and 3.25% in primary hospitals and ungraded hospitals, respectively. Anaesthesiologists were present in 91.20% of public hospitals and 8.80% of private hospitals. Anaesthesiologists were present in 83.55% general hospitals and 16.45% of specialised hospitals. The Heilongjiang Province has a total of 2041 operating rooms and 543 beds in recovery rooms. The number of anaesthesia cases per capita per year was 326.86. The percentages of anaesthesiologists' age ≥46, 36-45, 25-35 and <25 are 24.03%, 41.80%, 33.91% and 0.27%, respectively. The proportions of resident physicians and attending physicians were 60.87%, and the proportions of associate chief physicians and chief physicians were 39.13%. The proportions of anaesthesiologists working >12 hours, 10 hours≤time≤12 hours, 8 hours≤time<10 hours and <8 hours were 0.55%, 22.04%, 64.30% and 13.11%, respectively. CONCLUSIONS: The present study demonstrated for the first time that the proportion of anaesthesiologists in the Heilongjiang Province, China, is still insufficient. The structure of anaesthesiologists needs to be optimised.

Stellate ganglion block reduces inflammation and improves neurological function in diabetic rats during ischemic stroke.

Diabetes mellitus is an independent risk factor for ischemic stroke. Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes. Stellate ganglion block can effectively regulate the inflammatory response. Therefore, it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects. In this study, we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks. The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats. Subsequently, we performed left stellate ganglion block with 1% lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion. Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content. It also improved the recovery of neurological function, increased 28-day survival rate, inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats. However, injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block, whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect. We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke. These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway. We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.

Effects of rocuronium dosage on intraoperative neurophysiological monitoring in patients undergoing spinal surgery.

WHAT IS KNOWN AND OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) has been widely used in clinical practice. Therefore, the influence of neuromuscular blockers essential for spinal anaesthesia on IONM is worthy of our attention, but no randomized study has evaluated the dose-response effect. This study investigated the effects of different doses of rocuronium bromide on the intraoperative monitoring of motor evoked potentials (MEPs). METHODS: We conducted a randomized, double-blind trial to assess the effects of three rocuronium bromide doses (6.0, 9.0, 12 µg·kg-1 ·min-1 ) combined with intravenous infusion of propofol 6-8 mg·kg-1 ·h-1 and remifentanil 10 µg·kg-1 ·h-1 on the amplitudes of somatosensory evoked potentials (SEPs) and MEPs at the time of the baseline recording (T1 ), before pedicle screw placement (T2 ) and before spinal canal decompression (T3 ). Secondary outcomes included measurement of neuromuscular function, the occurrence of unexpected intraoperative body movement and recovery of spontaneous breathing. RESULTS AND DISCUSSION: A total of 123 patients were enrolled, and 120 patients were ultimately analysed. No differences were observed in the amplitude of SEPs among the three groups (p > 0.05). The MEP amplitude differences at T1 , T2 and T3 in all limbs did not differ in patients receiving rocuronium at 6.0 µg·kg-1 ·min-1 and 9.0 µg·kg-1 ·min-1 (p > 0.05). However, when rocuronium was administered at 12.0 µg·kg-1 ·min-1 , MEP amplitudes at the time point T3 were significantly attenuated compared with the time points T1 and T2 in both right upper limb and left lower limb (p = 0.002, p = 0.025, respectively). In patients treated with rocuronium 6.0 µg·kg-1 ·min-1 , the incidence of unexpected body movement was significantly higher (p = 0.026), and the train-of-four count (TOF count) showed a significant increase at T2 and T3 (p < 0.001) compared to other doses. WHAT IS NEW AND CONCLUSION: Rocuronium bromide at a rate of 9.0 µg·kg-1 ·min-1 provided suitable and adequate muscle relaxation without inhibiting IONM; thus, this dose is recommended for spinal surgery.

Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis.

BACKGROUND: Traumatic brain injury (TBI)-induced acute lung injury (ALI) is a critical condition, and inflammation and apoptosis play essential roles. Molecular hydrogen (H2) exerts anti-inflammatory and anti-apoptotic effects. Our previous work has shown that 42% H2 can improve TBI. In the current study, we tested the hypothesis that inhalation of hydrogen (42% H2, 21% O2, balanced nitrogen) for 1 h per day can improve TBI-induced ALI. METHODS: Sprague-Dawley male rats were randomly divided into 3 groups. Except for the sham group (group S), rats were subjected to a fluid percussion injury (FPI) and the H2 treatment group were given inhaled hydrogen for 1 h per day. We evaluated the lung function, pyroptosis and apoptosis at 24 h, 48 h and 72 h. RESULTS: Compared with group S, the rats in the TBI group (group T) showed obvious pulmonary edema after a TBI. Inhalation of high-concentration hydrogen significantly improved the rats. During this process, rats had some tendency to heal on their own, and H2 also accelerated the self-healing process. Lung injury scores, oxygenation index and pulmonary edema were consistent. Compared with group S, the pyroptosis-related proteins Caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and Gasdermin-D (GSDM-D) in the lung tissues of the rats in group T were significantly increased after a TBI. In the H2 treatment group (group H), these proteins were significantly decreased. The levels of IL-1ß and IL-18 were significantly increased after TBI while in group H were significantly decreased. At the same time, cleaved caspase-3 and BCL-2/Bax were also changed after H2 treatment. These demonstrates the powerful ameliorating effect of H2 on pyroptosis, apoptosis and systemic inflammation. However, rats also had tendency to heal on their own, and H2 also accelerated the self-healing process at the same time. CONCLUSIONS: H2 improves TBI-ALI, and the mechanism may be due to the decrease of both pyroptosis and apoptosis and the alleviation of inflammation. These findings provide a reference and evidence for the use of H2 in TBI-ALI patients in the intensive care unit (ICU).

Adiponectin ameliorates lung ischemia-reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia-reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. METHODS: High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. RESULTS: Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. CONCLUSION: These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.

Inhibition of nitric oxide synthase aggravates brain injury in diabetic rats with traumatic brain injury.

Studies have shown that hyperglycemia aggravates brain damage by affecting vascular endothelial function. However, the precise mechanism remains unclear. Male Sprague-Dawley rat models of diabetes were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin. Rat models of traumatic brain injury were established using the fluid percussion method. Compared with traumatic brain injury rats without diabetic, diabetic rats with traumatic brain injury exhibited more severe brain injury, manifested as increased brain water content and blood-brain barrier permeability, the upregulation of heme oxygenase-1, myeloperoxidase, and Bax, the downregulation of occludin, zona-occludens 1, and Bcl-2 in the penumbra, and reduced modified neurological severity scores. The intraperitoneal injection of a nitric oxide synthase inhibitor N(5)-(1-iminoethyl)-L-ornithine (10 mg/kg) 15 minutes before brain injury aggravated the injury. These findings suggested that nitric oxide synthase plays an important role in the maintenance of cerebral microcirculation, including anti-inflammatory, anti-oxidative stress, and anti-apoptotic activities in diabetic rats with traumatic brain injury. The experimental protocols were approved by the Institutional Animal Care Committee of Harbin Medical University, China (approval No. ky2017-126) on March 6, 2017.

Isoform-specific functions of c-Jun N-terminal kinase 1 and 2 in lung ischemia-reperfusion injury through the c-Jun/activator protein-1 pathway.

BACKGROUND: c-Jun N-terminal kinase 1 (JNK1) and JNK2 regulate distinct pathological processes in lung diseases. Here we discriminated the respective roles of these kinases in lung transplantation-induced ischemia-reperfusion injury (IRI). METHODS: Rat pulmonary microvascular endothelial cells were transfected with JNK1 small-interfering RNA (siRNA) and JNK2 siRNA and then subjected to in vitro IRI. For the isoform confirmed to aggravate IRI, the delivery of short-hairpin RNA (shRNA) plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. After a 3-hour reperfusion, the samples were collected. RESULTS: JNK1 siRNA decreased but JNK2 siRNA increased JNK phosphorylation and activity, phosphorylated and total c-Jun, and activator protein-1 activity. Although JNK1 siRNA decreased apoptosis and the levels of malondialdehyde, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α), it increased the levels of superoxide dismutase, S-phase percentage, and cyclin D1; JNK2 siRNA had a converse effect. JNK1 siRNA decreased the level of lactate dehydrogenase and increased the levels of VE-cadherin, nitric oxide, phosphorylated nitric oxide synthase, and cell viability; JNK2 si RNA had a converse effect. Compared with the control group, the JNK1 shRNA group exhibited a higher lung oxygenation index and lower lung apoptosis index, injury score, wet weight:dry weight ratio, and levels of IL-1, IL-6, and TNF-α. CONCLUSIONS: JNK1 aggravated, but JNK2 alleviated, IRI through differential regulation of the JNK1 pathway in in vitro ischemia-reperfusion. JNK1 silence attenuated lung graft dysfunction by inhibiting inflammation and apoptosis. These findings provide a theoretical basis for devising therapeutic strategies against IRI after lung transplantation.

Effects of a high concentration of hydrogen on neurological function after traumatic brain injury in diabetic rats.

Reactive oxygen species, inflammation, and apoptosis are major contributors to secondary injuries that follow traumatic brain injury (TBI) in diabetic patients. Hydrogen (H2) can selectively neutralize reactive oxygen species and downregulate inflammatory and apoptotic factors. Therefore, we investigated the effects of inhaled high and low concentrations of hydrogen on neurological function after TBI in diabetic rats and the potential mechanism. We found that the inhalation of high concentrations of H2 significantly improved outcomes following TBI in diabetic rats. The inhalation of 42% H2 for one hour per day for 48 h significantly reduced brain edema, decreased the extravasation of sodium fluorescein, and reduced oxidative stress markers (p < 0.05). In addition, the inhalation of a high concentration of H2 (42% for one hour per day for 7 days) improved neurological deficits (p < 0.05) and reduced the expression of apoptotic protein markers (p < 0.05). However, the inhalation of 3% H2 did not yield significant effects. These results showed that the inhalation of 42% H2 can alleviate nerve damage and improve neurological function after TBI in diabetic rats. Therefore, the inhalation of a high concentration of H2 may be associated with the treatment of traumatic brain injuries.

Serum metabolomics profiling and potential biomarkers of myopia using LC-QTOF/MS.

Myopia is the most common form of refractive eye disease, and the prevalence is increasing rapidly worldwide. However, the key metabolic alterations in individuals with high myopia are not understood clearly, and serum biomarkers remain to be determined. The objectives of this study were to identify serum biomarkers and investigate the metabolic alterations of myopia. The serum metabolomics profiling was investigated on 30 high myopia cases and 30 controls (without myopia) using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), and an independent additional cohort including 20 cases and 19 controls were investigated to validate potential metabolite candidates for biomarkers. According to the metabolic differences, the myopia patients and controls could be divided into different clusters and nine metabolites were found to be closely correlated with myopia. In the cohort of validation, eight metabolites were confirmed. Metabolic pathway analyses of these metabolites of high myopia involved abnormal phospholipid, diacylglycerol, amino acid, and vitamin metabolism, which were closely correlated with oxidative stress and inflammation. Multiple logistic regression analyses showed that γ-glutamyltyrosine and 12-oxo-20-trihydroxy-leukotriene B4 were potential biomarkers of myopia with a combined high sensitivity (97%), specificity (90%), and area under the curve value (0.983). These findings may contribute to an understanding of the pathophysiological changes and pathogenesis of myopia, and provide novel insight into the early prevention and control of high myopia.

Recent advances in the neuroprotective effects of medical gases.

Central nervous system injuries are a leading cause of death and disability worldwide. Although the exact pathophysiological mechanisms of various brain injuries vary, central nervous system injuries often result in an inflammatory response, and subsequently lead to brain damage. This suggests that neuroprotection may be necessany in the treatment of multiple disease models. The use of medical gases as neuroprotective agents has gained great attention in the medical field. Medical gases include common gases, such as oxygen, hydrogen and carbon dioxide; hydrogen sulphide and nitric oxide that have been considered toxic; volatile anesthetic gases, such as isoflurane and sevoflurane; and inert gases like helium, argon, and xenon. The neuroprotection from these medical gases has been investigated in experimental animal models of various types of brain injuries, such as traumatic brain injury, stroke, subarachnoid hemorrhage, cerebral ischemic/reperfusion injury, and neurodegenerative diseases. Nevertheless, the transition into the clinical practice is still lagging. This delay could be attributed to the contradictory paradigms and the conflicting results that have been obtained from experimental models, as well as the presence of inconsistent reports regarding their safety. In this review, we summarize the potential mechanisms underlying the neuroprotective effects of medical gases and discuss possible candidates that could improve the outcomes of brain injury.

Protection of Myocardial Ischemia-Reperfusion by Therapeutic Hypercapnia: a Mechanism Involving Improvements in Mitochondrial Biogenesis and Function.

Previous studies proposed that acidic reperfusion may be a protective strategy for myocardial ischemia-reperfusion therapy with potential of clinical transformation. In this study, we investigated whether therapeutic hypercapnia could mimic acidosis postconditioning in isolated hearts with a 30-min left coronary artery ligation-reperfusion model in rats. Therapeutic hypercapnia (inhalation 20% CO2 for 10 min) is cardioprotective with a strict therapeutic time window and acidity: it reduced the infarct ratio and serum myocardial enzyme and increased the myocardial ATP content. Furthermore, mitochondrial morphology damage, the loss of mitochondrial membrane potential, and the formation of mitochondrial permeability transition pore were effectively inhibited, indicating the improvements in mitochondrial function. The expression of the mitochondrial biogenesis regulators was upregulated simultaneously. These findings indicated therapeutic hypercapnia in animals can mimic ex vivo acidosis postconditioning to alleviate myocardial ischemia-reperfusion injury. The effect is related to improvement in mitochondrial function and regulation of the mitochondrial biogenesis pathway.

Therapeutic hypercapnia reduces blood-brain barrier damage possibly via protein kinase Cε in rats with lateral fluid percussion injury.

BACKGROUND: This study investigated whether therapeutic hypercapnia (TH) ameliorated blood-brain barrier (BBB) damage and improved the neurologic outcome in a rat model of lateral fluid percussion injury (FPI), and explored the possible underlying mechanism. METHODS: Rats underwent lateral FPI and received inhalation of 30%O2-70%N2 or 30%O2-N2 plus CO2 to maintain arterial blood CO2 tension (PaCO2) between 80 and 100 mmHg for 3 h. To further explore the possible mechanisms for the protective effects of TH, a PKC inhibitor staurosporine or PKCαß inhibitor GÖ6976 was administered via intracerebral ventricular injection. RESULTS: TH significantly improved neurological function 24 h, 48 h, 7 d, and 14 d after FPI. The wet/dry ratio, computed tomography values, Evans blue content, and histological lesion volume were significantly reduced by TH. Moreover, numbers of survived neurons and the expression of tight junction proteins (ZO-1, occludin, and claudin-5) were significantly elevated after TH treatment at 48-h post-FPI. TH significantly increased the expression of protein kinase Cε (PKCε) at 48-h post-FPI, but did not significantly change the expression of PKCα and PKCßII. PKC inhibitor staurosporine (but not the selective PKCαß inhibitor-GÖ6976) inhibited the protective effect of TH. CONCLUSIONS: Therapeutic hypercapnia is a promising candidate that should be further evaluated for clinical treatment. It not only protects the traumatic penumbra from secondary injury and improves histological structure but also maintains the integrity of BBB and reduces neurologic deficits after trauma in a rat model of FPI.

Identification of Potential Biomarkers and Metabolic Profiling of Serum in Ovarian Cancer Patients Using UPLC/Q-TOF MS.

BACKGROUND/AIMS: Ovarian cancer (OC) is a malignant neoplasm of the female reproductive system with a high mortality rate. Identifying useful biomarkers and clarifying the molecular pathogenesis of OC are critical for early diagnosis and treatment. The aim of the study was to identify candidate biomarkers and explore metabolic changes of OC. METHODS: A two-stage design was used in our study, with a discovery cohort of OC cases (n = 30) and controls (n = 30) and an independent cohort of cases (n = 17) and controls (n = 18) for validation. The serum metabolic profiling was investigated by ultra-performance liquid chromatography and quadrupole time-of-fight mass spectrometry with positive electrospray ionization. RESULTS: A total of 18 metabolites closely related to OC were identified in the discovery stage, of which 12 were confirmed in the validation cohort. Metabolic pathways in OC related to these biomarkers included fatty acid ß-oxidation, phospholipid metabolism, and bile acid metabolism, which are closely related to the proliferation, invasion, and metastasis of cancer cells. Multiple logistic regression analysis of these metabolites showed that 2-piperidinone and 1-heptadecanoylglycerophosphoethanolamine were potential biomarkers of OC, with high sensitivity (96.7%), specificity (66.7%), and area under the receiver operating characteristic curve value (0.894). CONCLUSION: These findings provide insight into the pathogenesis pathogenesis of OC and may be useful for clinical diagnosis and treatment.

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.

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood-brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

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.

Effects of Propofol on Excitatory and Inhibitory Amino Acid Neurotransmitter Balance in Rats with Neurogenic Pulmonary Edema Induced by Subarachnoid Hemorrhage.

INTRODUCTION: Propofol exhibits neuroprotective effects mediated by the inhibition of excitatory amino acid (EAA) neurotransmitter release and potentiation of inhibitory amino acid (IAA) neurotransmitters. To our knowledge, this is the first study to investigate the effects of propofol on the EAA and IAA balance in neurogenic pulmonary edema (NPE). METHODS: Sixty male Wistar rats were randomized to Sham, NPE, Low-dose propofol, and High-dose propofol groups. NPE was induced via rapid injection of autologous blood (0.5 ml) into the cisterna magna. The Low- and High-dose propofol groups were pretreated with boluses of 2 and 5 mg kg(-1), respectively, prior to blood injection, followed by continuous propofol infusion at 6 and 15 mg kg(-1) h(-1), respectively. The mean arterial pressure (MAP), heart rate, intracranial pressure (ICP), peak inspiratory pressure (PIP), and arterial blood gases were continuously recorded. After 2 h, the lung wet-to-dry weight ratio, total protein concentration in the bronchoalveolar lavage fluid (BALF), brain water content, cortical EAA and IAA levels, chest X-ray, and histological staining of lung sections were evaluated. RESULTS: Blood injections into the cisterna magna induced NPE and hemodynamic changes. Propofol alleviated the increases in the MAP, ICP, and PIP, improved oxygenation and histopathological changes, ameliorated pulmonary and cerebral edema, increased the IAA brain levels, and decreased the ratio of Glu to γ-aminobutyric acid. CONCLUSIONS: The current findings suggest that propofol improves NPE likely via IAA accumulation and the regulation of EAA and IAA balance, which may represent an effective treatment for NPE.