Microbubble-Enhanced Transdermal Drug Delivery Sonoelectric Patch.

Transdermal drug delivery systems are highly appealing as a convenient drug delivery manner applicable to a wide variety of drugs. While most delivery relies on only passive diffusion and suffers low transdermal efficiencies. Ultrasound motivation promotes drug transdermal penetration but still calls for improvement, because only a thin proportion of the ultrasound energy is applied on the drug delivery patch and most ultrasound energy is wasted in deeper portions of biotissues. In this work, we develop a transdermal patch for enhanced drug delivery. The combination of microsized air pockets and the piezoelectric soft structure enable the conversion of an intended proportion of ultrasound energy into electric energy. The intensified drug flow and synergistic ultrasound pressure and electric field function simultaneously to enhance drug transdermal delivery. The delivery efficacy is related to the power of the ultrasound motivation, the size of the microscopic air pockets, and the chemical structure of the drug molecules. The temperature of the patch within the delivery process remains in the safe range, and the mild temperature elevation causes color changes of the thermochromic patch, used to indicate effective ultrasound-patch matching. A model delivery patch for pain release is constructed, and animal experiments indicate that the drug blood concentrations are 100% higher than the delivery using only ultrasound and even more remarkably enhanced when compared to only electric-field-motivated delivery or static delivery without external motivations.

Personalized 3D Printed Tooth-Supported Template as a Novel Strategy for Radiofrequency Thermocoagulation for Trigeminal Neuralgia After the Failure of CT-Guided Puncture.

Background: Trigeminal neuralgia (TN) is a common form of craniofacial pain, and Radiofrequency thermocoagulation (RFT) has become a commonly utilized treatment modality for TN. However, the complex anatomical configuration of the maxillofacial region and the difficulties inherent in positioning the neck in a hyperextended manner can present challenges for CT-guided punctures. Aim: The objective of this study is to assess the effectiveness and safety of 3D printed tooth-supported template(3D-PTST) guided RFT in patients who have previously undergone unsuccessful CT-guided puncture. Methods: Patients with TN undergoing RFT at the Department of Pain Medicine, PLA General Hospital, from January 2018 to January 2023, were assessed. 3D-PTST guided RFT was employed as an alternative when percutaneous puncture failed. Clinical, demographic, and follow-up data were collected. The duration of the procedure was determined by subtracting the time of anesthesia administration from the time of surgical drape removal. Pain intensity was assessed using the Numerical Rating Scale-11 scale. Treatment effects were evaluated utilizing the Barrow Neurological Institute scale. Incidences of complications related to RFA were documented. Results: Six TN patients underwent 3D-PTST guided RFT. With tooth-supported template guidance, five patients achieved therapeutic target puncture in one attempt with one CT scan. One patient required two attempts with two CT scans. Operation duration ranged from 18 to 46 mins (mean 30 mins). All completed 3D-PTST-guided RFT without difficulty, significantly improving pain symptoms. Four patients had no pain recurrence at 12, 18, 36 and 37 months follow-up, respectively. Recurrence occurred in two patients (at 1 and 13 months). No serious treatment-related complications were observed. Conclusion: 3D-PTST guided RFT is an effective, repeatable, safe, and minimally invasive treatment method for patients with TN who have failed due to difficulty in puncture.

Long-Term Follow-Up of Ultrasound-Guided Glossopharyngeal Nerve Block Treatment for Glossopharyngeal Neuralgia: A Retrospective Clinical Study of 43 Cases.

Background: Glossopharyngeal neuralgia (GPN) is a rare chronic neuropathic pain disorder that significantly impacts quality of life. Ultrasound-guided glossopharyngeal nerve blocks (UGPNB) have gained popularity due to their various advantages. However, there have been no studies reporting the long-term outcomes of UGPNB in a larger cohort of GPN patients. Aim: This study aims to evaluate the efficacy and safety of UGPNB in patients with GPN. Methods: We reviewed the electronic medical records of patients with GPN who received UGPNB at the Department of Pain Medicine of the First Medical Center, PLA General Hospital between June 1, 2011, and June 1, 2022. The effect of UGPNB was evaluated using the Barrow Neurological Institute (BNI) scale. Improvement was defined as a reduction in pain category by comparing pain categories before and after therapy. Recovery was defined as achieving BNI I after treatment. Patients who responded to treatment but then regressed to the category before therapy were considered to have experienced pain relapse. Results: A total of 43 patients with GPN who received UGPNB were included in the analysis. At discharge, 35 (81.4%) patients experienced pain improvement after treatment, and among them, 13 (30.2%) patients achieved recovery. After discharge, 13 patients (37.1%) out of the 35 effective patients experienced pain relapse at different time intervals: 0.5, 0.7, 1, 1, 3, 3, 4, 12, 15, 36, 45, 63, and 96 months. The cumulative recurrence-free survival rates were 88.85% at month 1, 82.83% at month 3, 77.04% at month 12, 70.31% at month 36, and 54.66% at month 120. Among the 13 patients who experienced relapse, four patients received a second UGPNB treatment, and pain improved in two patients (50%). No severe adverse reactions were documented. Conclusion: UGPNB is an effective, repeatable, safe, and minimally invasive treatment for patients with GPN. It may be preferable to consider UGPNB before undergoing invasive intracranial surgery or neurodestructive methods.

Piezoionic High Performance Hydrogel Generator and Active Protein Absorber via Microscopic Porosity and Phase Blending.

Generating electricity in hydrogel is very important but remains difficult. Hydrogel with electricity generation capability is more capable in bio-relevant tasks such as tissue engineering, artificial skin, or medical treatment, because electricity is indispensable in regulating physiological activities. Here, a porous and phase blending hydrogel structure for effective piezoionic electricity generation is developed. Dynamic electric field is generated taking advantage of the difference in streaming speeds of sodium and chloride in the material. Microscopic porosity and hydrophilic-hydrophobic phase blending are the two key factors for prominent piezoionic performance. Voltages as high as 600 mV are first realized in hydrogels in response to medical ultrasound stimulation. The hydrogel structure is also subjective to effective substance exchange and can actively enrich proteins from surroundings under mechanical stimuli. Preliminary applications in neural stimulation, constructing complex spatial-temporal chemical and electric field distribution patterns, mimetic tactile sensor, sample pretreatment in fast detection, and enzyme immobilization are demonstrated.

Low BMI, blood calcium and vitamin D, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Aim: To explore the risk factors of osteoporosis in postmenopausal women in China. Method: This study collected all patient data from January 2014 to December 2015. Basic information and questionnaires were collected from 524 postmenopausal women in Sanya and Hainan Province. The questionnaire was administered to the enrolled participants by endocrinologists. Biochemical parameters were measured using fasting blood samples, and bone density was measured by dual energy X-ray absorptiometry at the department of radiology of Hainan hospital, PLA General Hospital. Participants with an R-value of ≤-2.5 were diagnosed with osteoporosis. After deleting missing values for each factor, 334 participants were divided into the osteoporosis (n=35) and non-osteoporosis (n=299) groups according to the R-values. Results: The participants had a median age of 60.8 years (range: 44-94 years). Among the 334 postmenopausal women included in this study, 35 (10.5%) were diagnosed with osteoporosis. Univariate analysis showed statistically significant differences in age, BMI, type of work, alkaline phosphatase, years of smoking, blood calcium levels, kyphosis, fracture, and asthma between the two groups (P<0.05). In addition, multivariate logistic analysis showed that age (odds ratio [OR]: 1.185, 95% confidence interval [CI]: 1.085-1.293, P<0.001) and kyphosis times (OR:1.468, 95% CI: 1.076-2.001, P=0.015) were positively correlated with postmenopausal osteoporosis, whereas BMI (OR: 0.717, 95% CI: 0.617-0.832, P<0.001), blood calcium levels (OR: 0.920, 95% CI: 0.854-0.991, P=0.027), vitamin D levels (OR: 0.787, 95% CI: 0.674-0.918, P=0.002), and outdoor activity time (OR: 0.556, 95% CI: 0.338-0.915, P=0.021) were negatively correlated with postmenopausal osteoporosis. Conclusion: Low BMI, blood calcium and vitamin D levels, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD-induced menopausal mice.

AIMS: As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin. METHODS: Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins. RESULTS: The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons. CONCLUSION: Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

Inhibition effect of choline and parecoxib sodium on chronic constriction nerve injury-induced neuropathic pain in rats.

PURPOSE: The simultaneous use of drugs with different mechanisms of analgesic action is a strategy for achieving effective pain control while minimizing dose-related side effects. Choline was described to potentiate the analgesic action of parecoxib sodium at small doses in several inflammatory pain models. However, these findings are still very limited, and more associated data are required to confirm the effectiveness of the combined choline and parecoxib sodium therapy against inflammatory pain. METHODS: Adult rats were randomly divided into 9 groups (N = 6/group). The sham surgery group received an intraperitoneal (i.p.) injection of saline. Rats with chronic constriction injury (CCI) of the sciatic nerve received saline, choline (cho, 6, 12 and 24 mg/kg), parecoxib sodium (pare, 3, 6, and 12 mg/kg), or a combination of choline 6 mg/kg and parecoxib sodium 3 mg/kg. Mechanical and heat pain thresholds were measured at 30 min after drug treatment at Days 3, 5, 7, 10, and 14 after CCI. Another 30 rats were divided into 5 groups (N = 6/group): the sham, CCI + saline, CCI + cho-6 mg/kg, CCI + pare-3 mg/kg, and CCI + cho-6 mg/kg + pare-3 mg/kg groups. After repeated drug treatment for 7 days, five rats were randomly selected from each group, and the lumbar dorsal root ganglia (DRGs) (L4-6) were harvested for western blot analysis. RESULTS: Choline significantly attenuated mechanical and heat hypersensitivity in CCI rats at 12 and 24 mg/kg doses (P < 0.05) but was not effective at the 6 mg/kg dose. Parecoxib sodium exerted significant pain inhibitory effects at the 6 and 12 mg/kg doses (P < 0.05) but not at the 3 mg/kg dose. Combining a low dose of choline (6 mg/kg) and parecoxib sodium (3 mg/kg) produced significant pain inhibition in CCI rats and reduced the expression of high mobility group protein 1 (HMGB1) and nuclear factor-kappa Bp65 (NF-κBp65) in L4-6 DRGs. CONCLUSION: 1. In a rat model of chronic neuropathic pain (CCI), at a certain dose, choline or parecoxib sodium can alleviate mechanical pain and thermal hyperalgesia caused by CCI. 2. The combination of choline and parecoxib sodium in nonanalgesic doses can effectively relieve neuropathic pain, and its mechanism may be related to the inhibition of the high mobility group protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway.

Risk Factors and a Nomogram for Prediction of Refractory Pudendal Neuralgia: A Retrospective Multivariate Analysis Study.

BACKGROUND: Pudendal neuralgia (PN) is one of the most common forms of genital pain. About 4% or higher of patients suffering from chronic pain. OBJECTIVES: The aim of this study was to evaluate the risk factors for prediction of refractory PN (RPN). STUDY DESIGN: A retrospective multivariate analysis study. SETTING: This retrospective analysis included 112 patients with PN who received the pudendal nerve block treatment at the Pain Department of General Hospital of People's Liberation Army. METHODS: Univariate and multivariable logistic regression analyses were used for covariates selection. A nomogram was developed to estimate nonresponse to the pudendal nerve block. RESULTS: The median age of patients and duration of patients were 48.0 and 1.25 years, respectively. Among 112 patients, there were 64 good responders to the pudendal nerve block for neuropathic pain and 48 nonresponders. Multivariate analysis of 112 patients with PN demonstrated high self-rating depression scale scores (> 32) (odds ratio [OR], 95% confidence interval [CI]: 0.11, 0.01-0.77), damage to more than 2 terminal branches (OR, 95% CI: 0.22, 0.07-0.71), sensory deficit at S2-S4 on the dermatome map (OR, 95% CI: 0.22, 0.05-0.90), and duration of pain (> 4 years) (OR, 95% CI: 0.10, 0.03-0.42) were significant prognostic factors for nonresponse to the pudendal nerve block. LIMITATIONS: There are information biases for retrospective analysis, thus making it more difficult to come up with definitive conclusions. Large-scale randomized clinical trials are warranted to evaluate the risk factors for prediction of RPN. CONCLUSIONS: A longer duration of pain was correlated with a worse prognosis of the neurological disease. Patients with depression were prone to nonresponse to the pudendal nerve block treatment. Pain involved in more than 2 terminal branches and small fibers, affected at S2-S4 dermatome map, were considered to poor prognosis.

Preoperative malnutrition as an independent risk factor for the postoperative mortality in elderly Chinese individuals undergoing hip surgery: a single-center observational study.

Objective: Malnutrition is prevalent in elderly with hip fracture and higher than in community-dwelling older adults. Scarce studies have examined the association between preoperative malnutrition and postoperative mortality in elderly Chinese individuals with hip fracture. This study was designed to explore the effect of preoperative malnutrition on the postoperative long-term mortality in elderly Chinese individuals undergoing hip surgery. Methods: As a single-center observational study, this study included 263 consecutive patients above 70 years old with hip fracture and elective surgery. Preoperative nutritional status was evaluated by prognostic nutritional index (PNI). Patients were divided into one group with malnutrition (26 patients with PNI ⩽ 38) and the other group without malnutrition (169 patients with PNI > 38), respectively. Results: The overall malnutrition rate was 13.3% (26 patients). The postoperative long-term mortality rates of patients with and without malnutrition had statistically significant difference [10 patients (38.5%) and 32 patients (18.9%), p < 0.05]. Cox regression analysis showed that malnutrition (hazard ratio: 0.269, 95% confidence interval: 0.085-0.859, p < 0.05) and partial pressure of carbon dioxide (hazard ratio: 0.873, 95% confidence interval: 0.790-0.964, p < 0.05) were independent risk factors for the postoperative long-term mortality. Conclusion: This study demonstrated that preoperative malnutrition was an independent risk factor for the postoperative long-term mortality and resulted in a more than 2.5-fold increase of the postoperative long-term mortality in elderly Chinese individuals undergoing hip surgery.

Sacral Nerve Stimulation in Patients With Refractory Pudendal Neuralgia.

BACKGROUND: Pudendal neuralgia (PN) is one of the most common forms of genital pain. Only 42.2% of PN patients respond to the first-line treatment. Novel neuromodulation techniques in the treatment of refractory PN patients are urgently required. OBJECTIVES: The aim of this study was to evaluate the treatment effects and adverse events of sacral nerve stimulation (SNS) for patients with refractory PN. STUDY DESIGN: A prospective nonrandomized study. SETTING: This prospective analysis included 33 patients who received the phase II surgical implantation. METHODS: A total of 55 eligible PN patients were recruited for SNS treatment after informed consent, and 33 of 55 patients with a minimum 50% improvement were candidates for surgical implantation. Visual Analog Scale (VAS) scores, Self-rating Anxiety and Depression Scale, Quality of life score (SF-36), and sleep monitoring indicators before and after surgery were used to assess the effects of SNS on patients with refractory PN. RESULTS: Thirty-three patients were included in the final analysis, involving 24 women and 9 men with a mean age of 49.5 years (26-70 years). There was a favorable decrease in pain severity (VAS scores) from 7.1 ± 1.1 at baseline to 6.1 ± 1.0 on postoperative day 1, and 2.8 ± 0.7 at 1 week, 1.7 ± 0.5 at 1 month, 1.1 ± 0.7 at 6 months, and 1.0 ± 0.6 at 12 months after surgery, respectively (P < 0.05). The mean score of each section of SF-36 after SNS was significantly higher than that at baseline (P < 0.05). Total sleep time and sleep time in each period were significantly prolonged after SNS implantation compared with that before surgery (6 months vs Pre, total: 5.32 ± 1.49 hours vs 3.66 ± 1.19 hours, deep: 2.52 ± 0.63 hours vs 1.36 ± 0.43 hours, light: 1.78 ± 0.42 hours vs 0.99 ± 0.30 hours, rapid eye movement: 1.41 ± 0.29 hours vs 0.89 ± 0.27 hours, P < 0.05). No serious device complications were reported during the follow-up period. LIMITATIONS: Large-scale randomized clinical trials are warranted to evaluate the risk factors for prediction of refractory PN. CONCLUSIONS: These data imply that SNS can have beneficial effects on patients with refractory PN.

The immunometabolite S-2-hydroxyglutarate exacerbates perioperative ischemic brain injury and cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity.

BACKGROUND: Metabolic dysregulation and disruption of immune homeostasis have been widely associated with perioperative complications including perioperative ischemic stroke. Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction. METHODS: Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice 1 day after ileocecal resection. CD8+ T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8+ T lymphocytes after ischemia. CD8+ T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1-/-) stroke mice. RESULTS: The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8+ T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8+ T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8+ T cells, in which S-2HG is more abundant. S-2HG alters CD8+ T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity. CONCLUSION: Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8+ T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.

How Should Anesthesiologists Face Coronavirus Disease 2019?

Coronavirus disease 2019 (COVID-19) is a highly contagious disease. Most infected patients manifest mild flu-like symptoms, but in some cases, the patients rapidly develop severe lung infections and pneumonia. It is estimated that about 15-20% of patients with COVID-19 develop hypoxemia and require some form of oxygen therapy and ventilation support. Further, exacerbation of the disease usually requires an emergency tracheal intubation, where the patients are more prone to coughing and aerosol diffusion, placing the anesthesiologist at an extremely high risk of infection. In this review, after a brief introduction to the epidemiology and pathogenesis of the COVID-19, we describe various recommendations that the anesthesiologists should employ to avoid the chances of infection during the management of severely ill patients. We describe key steps such as not removing the patient's mask prematurely and using sedatives, analgesics, and muscle relaxants for rapid and orderly intubation. The use of spinal cord and regional nerve block anesthesia should also be promoted to avoid general anesthesia. Since the patients with COVID-19 may also have disorders related to other parts of the body (other than lungs), short-acting drugs are recommended to actively maintain the perfusion pressure of the peripheral and important organs without metabolism of the drugs by the liver and kidney. Multimodal analgesia is advocated, and non-steroidal anti-inflammatory analgesic drugs can be used appropriately. In this review, we also discuss key studies and experiences of anesthesiologists from China, highlights research findings, and inform on the proper management of patients with perspective on anesthesiologists.

Synergistically Active Piezoelectrical H2 O2 Production Composite Film Achieved from a Catalytically Inert PVDF-HFP Matrix and SiO2 Fillers.

Local and decentralized H2 O2 production via a piezoelectrical process promises smart biological utilization as well as environmental benefits. However, stable, bio/environmentally safe, and easily applied H2 O2 generation materials are still lacking. Here, we report a novel flexible H2 O2 generation polymeric film composed of catalytically inert PVDF-HFP (Poly(vinylidene fluoride-co-hexafluoropropylene)) matrix and SiO2 nanoparticle fillers. The film is bio-/environmentally benign at resting states, but effectively produces H2 O2 upon ultrasonic motivation at a production rate of 492 µmol g SiO 2 - 1 in one hour. Experimental and simulation methods in combination indicate that the effective H2 O2 generation capabilities stem from the synergistic existence of piezoelectrical fields and the air-liquid-solid three-phase regions around the porous film. The chemical conversions are motivated by the adsorbed charges. The silicon hydroxyl groups properly stabilize the *OOH intermediate and facilitate the chemical conversions of 2e- ORR of ambient O2 . We expect the report to inspire H2 O2 piezoelectrical generation materials and promote the novel production strategies of H2 O2 as well as piezoelectrical functional materials.

Delayed Recovery After Deep Brain Stimulation Surgery for Parkinson's Disease Under General Anesthesia-Cases Report.

Objective: Parkinson's disease (PD) is a neurodegenerative syndrome, and deep-brain stimulation (DBS) is an effective therapy for carefully screened patients with PD. However, delayed recovery after anesthesia, which occurs after taking prolonged general anesthesia for such patients, has been reported less frequently in literature. This report explores the possible causes of postoperative awakening delay in patients undergoing DBS surgery due to general anesthesia and provides a reference for anesthesia management of similar operations in the future. Case Presentation: Three patients with PD elective underwent DBS surgery. The first patients demonstrated walking disability, gait deficits, unstable posture, limb stiffness, and imbalance. The second demonstrated left limb static tremor, stiffness, and bradykinesia. The third demonstrated bradykinesia, rigidity, walking deficits, and decreased facial expression. These included two males and one female with a mean patient age of 60.7 ± 6.7year, weight of 63.7 ± 11 kg, the height of 163.3 ± 7.6 cm, and preoperative American Society of Anesthesiology rating of 2.3 ± 0.6. The preoperative Glasgow Coma Scale mean score was 15. All patients completed the operation under general anesthesia (the mean anesthesia time was 5.3 ± 1.1 h). The mean operation time was 252 ± 60 min. The mean bleeding volume was 50 ml, and the urine volume was 867 ± 569 ml. However, all the patients showed unconsciousness after 95 ± 22 min after stopping the anesthetic, and the respiratory function was in good condition, but they could not cooperate with anesthesiologists and had no response to the anesthesiologist's instructions. The mean hospital stay was 17 ± 7 days. All patients were discharged uneventfully. The average number of days patients followed up postoperatively was 171 ± 28.5 days. Motor and speech were improved significantly postoperatively in three patients compared with preoperatively. Taking anti-Parkinson medication was markedly reduced. There were no complications during postoperative follow-up. Conclusions: To prevent delayed recovery occurring after DBS surgery in Parkinson's disease, it is recommended to take scalp nerve block + general anesthesia to complete the procedure while avoiding general anesthesia.

Isoflurane alleviates hypoxia/reoxygenation induced myocardial injury by reducing miR-744 mediated SIRT6.

BACKGROUND: The objective of this study was to investigate the role of miR-744 and its target genes in ISO protection against hypoxia/reoxygenation (H/R) induced myocardial injury. METHODS: Rat cardiomyocytes H9c2 was used to establish an H/R model in vitro, and the level of miR-744 mRNA was detected by fluorescence quantitative PCR. CCK-8 and flow cytometry was used to detected cell viability and apoptosis. Myocardial injury markers CK-MB, cTnI, and LDH were detected by enzyme-linked immunosorbent assay (ELISA). Online bioinformatics software miRDB and miRWalk predicts miR-744 target and its potential binding site, and verifies the target by luciferase reporter assay. RESULTS: After H/R induction, miR-744 mRNA level was remarkedly increased, cell viability was deceased, and apoptosis was increased (p < 0.05). Myocardial injury markers CK-MB, cTnI, and LDH expressions were also increased (p < 0.05). However, ISO pretreatment can significantly alleviate the decrease in cell viability induced by H/R, the increase of cell apoptosis, and the increase of myocardial injury markers, and it play a cardioprotective effect (p < 0.05). More importantly, elevated miR-744 remarkedly weakened the protective effect of ISO on H/R-induced myocardial injury, resulting in decreased cell viability, increased apoptosis, and elevated concentration of myocardial injury indicators (p < 0.05). Luciferase reporter assay confirmed that Sirtuins6 (SIRT6) is a potential target of miR-744 and decreased in H/R-induced myocardial injury, and ISO exposure can reverse its level (p < 0.05). CONCLUSION: Our findings provide new insights that ISO pretreatment can remarkedly regulate miR-744 and its downstream target SIRT6 to mitigate myocardial injury induced by H/R.

Effect of operative trauma and multiple propofol anesthesia on neurodevelopment and cognitive function in developmental rats.

To investigate the effect of multiple propofol anesthesia and operative trauma on neuroinflammation and cognitive function in development rats and its mechanism. A total of 104 13-day-old neonatal Sprague-Dawley rats were randomly divided into 4 groups with 26 rats in each group: control group was treated with saline q.d for propofol group was treated with propofol q.d for surgery group received abdominal surgery under local anesthesia and then treated with saline q.d for surgery with propofol group received propofol anesthesia plus abdominal surgery under local anesthesia with ropivacaine at d1, then treated with propofol q.d for At d2 of experiment, 13 rats from each group were sacrificed and brain tissue samples were taken, the concentration of TNF-α in hippocampus was detected with ELISA, the expression of caspase-3 and c-fos in hippocampal tissue was determined with immunohistochemical method, the number of apoptotic neurons in hippocampus was examined with TUNEL assay. Morris water maze test was used to examine the cognitive function of the rest rats at the age of 60 d, and the TNF-α concentration, caspase-3, c-fos expressions and the number of apoptotic neurons in hippocampus were also detected. Compared with control group, TNF-α concentration, caspase-3, c-fos expression and the neuroapoptosis in hippocampus increased significantly in other three groups (all <0.05). Compared with surgery group, propofol group and surgery with propofol group showed increased TNF-α level, caspase-3 and c-fos expressions and apoptotic cell numbers (all <0.05), but there was no significant difference between last two groups (all >0.05). Morris water maze test showed that there were no significant differences in swimming speed, escape latency, target quadrant residence time and crossing times among groups (all >0.05). TNF-α level, expressions of caspase-3 and c-fos and apoptotic cell numbers in hippocampus had no significant differences among the 4 adult rats groups (all >0.05). Abdominal surgery and multiple propofol treatment can induce neuroinflammation and neuroapoptosis in hippocampus of neonatal rats, however, which may not cause adverse effects on neurodevelopment and cognitive function when they grown up.

Intraoperative Vitamin C Reduces the Dosage of Propofol in Patients Undergoing Total Knee Replacement.

PURPOSE: Propofol is commonly used as an intravenous anesthetic in surgical patients. However, its usage is associated with adverse effects. Auxiliary medication can reduce the dose of intravenous anesthetics. Hence, we investigated whether vitamin C could lower propofol dosage in elderly patients undergoing total knee replacement surgery. PATIENTS AND METHODS: The trial was carried out in PLA General Hospital in Beijing, China. We enrolled patients aged ≥50 years who were undergoing unilateral total knee arthroplasty with total intravenous anesthesia combined with lumbar sciatic nerve block. The patients were randomly assigned to either the vitamin C (Vc) group (0.067 g/kg) or the control group (an equivalent dose of normal saline). Nerve block was done for all the patients before the general anesthesia. The same depth of anesthesia was maintained during the operation. We compared the propofol dosage and adverse events (eg hypotension) during anesthesia between the two groups. This study was registered with the Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-16010112. RESULTS: There were significant differences in the total infusion dose (Vc group: 704.3 ± 188.6 mg; control group: 888.6 ± 232.7 mg; p = 0.016) and the average maintenance dose of propofol (Vc group: 5.8 ± 1.0 mg/kg/h; control group: 6.9 ± 1.6 mg/kg/h; p = 0.013). But there were no significant differences in the induction dose of propofol (control group: 90 mg, range 80-115 mg; Vc group: 100 mg, range 90-110 mg, p = 0.379) between the Vc and control groups. Furthermore, there were no significant differences in the hemodynamics and the incidence of intraoperative hypotension. CONCLUSION: Vitamin C can reduce the dosage of propofol in patients undergoing total knee replacement.

Isoflurane Alleviates Myocardial Injury Induced by Hypoxia/Reoxygenation by Regulating miR-18a-5p.

The protective effect and mechanism of isoflurane on myocardial injury was investigated by constructing in vitro hypoxia/reoxygenation (HR) cell model. HR cell models were established in vitro and treated with isoflurane (ISO). qRT-PCR was used to detect the relative expression of miR-18a-5p. CCK-8 kit and flow cytometry were performed to evaluate cell proliferation and apoptosis. The myocardial injury related markers, such as Cκ-MB, cTnI and LDH were detected by ELISA. Luciferase reporter gene assay was used to verify the interaction between miR-18a-5p and target genes. The expression of miR-18a-5p was significantly increased in hypoxic cardiomyocytes compared with control group (P < 0.001). Meanwhile, cardiomyocytes in the HR group showed inhibition of proliferation, a significant increase in cell apoptosis and in myocardial injury indicators, such as Cκ-MB, cTnI and LDH (P < 0.001). However, 1% ISO treatment alleviated myocardial cell injury induced by HR. Transfection of miR-18a-5p under ISO reduced the protective effect of 1% ISO against myocardial cell damage. Luciferase report gene assay confirmed that CCND2 might be the target gene of miR-18a-5p. In the in vitro cell model of myocardium, ISO alleviated cardiomyocyte injury caused by hypoxia/reoxygenation by down-regulating the expression of miR-18a-5p.

[Maximum dose of continuous infusion of mivacurium for thyroid surgery under total intravenous anesthesia: a sequential trial of monitoring neurological function in 30 patients].

OBJECTIVE: To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA). METHODS: Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 µg · kg-1 · min-1. The infusion rate was adjusted in the next patient based on the response of the previous patient in IONM. The depth of anesthesia was maintained with propofol and remifentanil during the surgery. The EC50 and 95%CI of mivacurium were calculated with Brownlee's up- and-down sequential method. During the operation, body movement and skin flushing of patient was monitored, and the mean arterial pressure (MAP) and heart rate (HP) were recorded immediately (T0) and at 5 min (T1) after injection of muscle relaxant for anesthesia induction, immediately (T2) and at 10 min (T3) and 20 min (T4) after initiation of intraoperative infusion of the muscle relaxant. RESULTS: The EC50 for continuous infusion of mivacurium without affecting IONM was 18.9 µg · kg-1 · min-1(95%CI: 17.3-20.5 µg · kg-1 · min-1) during thyroid surgery under TIVA. One patient (3.3%) developed transient facial skin redness after induction. Intubation difficulties or body motions occurred in none of the patients during the surgery. Pair-wise comparison showed no significant variations in MAP or HR of the patients at the 5 time points (P>0.05). CONCLUSIONS: In patients undergoing thyroid surgery under TIVA, the EC50 for continuous infusion of mivacurium is 18.9 µg · kg-1 · min-1 (95%CI: 17.3-20.5 µg · kg-1 · min-1), which does not affect IONM or causes serious adverse reactions during the operation.

Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats.

OBJECTIVE: Propofol is one of the most commonly used intravenous drugs to induce and maintain general anesthesia. In vivo and in vitro studies have shown that propofol can affect neuronal growth, leading to apoptosis and impairing cognitive function. The Abelson nonreceptor tyrosine kinase (c-Abl) is associated with both neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and other neurodegenerative diseases. This study aimed to explore the effect of propofol on apoptosis and neurocognition through its regulation of c-Abl expression in vivo and in vitro. MATERIALS AND METHODS: In this study, primary hippocampal neurons were cultured and exposed to propofol at different concentrations. Protein expression was measured by Western blotting and coimmunoprecipitation. The c-Abl transcription level was verified by fluorescence quantitative PCR. Reactive oxygen species (ROS) levels were detected by flow cytometry. In addition, an animal experiment was conducted to assess neuronal apoptosis by immunofluorescence staining for caspase-3 and to evaluate behavioral changes by the Morris water maze (MWM) test. RESULTS: The in vitro experiment showed that propofol significantly decreased c-Abl expression and ROS levels. In addition, propofol has no cytotoxic effect and does not affect cell activity. Moreover, in the animal experiment, intraperitoneal injection of 50 mg/kg propofol for 5 days obviously decreased the expression of c-Abl in the neonatal rat brain (p < .05) but did not significantly increase the number of caspase-3-positive cells. Propofol treatment did not significantly reduce the number of platform crossings (p > .05) or prolong the escape latency of neonatal rats (p > .05) in the MWM test. CONCLUSIONS: The present data suggest that reduced expression of this nonreceptor tyrosine kinase through consecutive daily administration of propofol did not impair learning or memory function in neonatal rats.