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Objective: Severe neurologic complications after spinal anesthesia are rare but highly distressing, especially in pregnant women. Bupivacaine is widely used in spinal anesthesia, but its neurotoxic effects have gained attention. Methods: Furthermore, the etiology of bupivacaine-mediated neurotoxicity in obstetric patients re- mains unclear. Female C57BL/6 mice were intrathecally injected with 0.75% bupivacaine on the 18th day of pregnancy. We used immunohistochemistry to examine DNA damage after bupivacaine treat- ment in pregnant mice and measured γ-H2AX (Ser139) and 8-OHdG in the spinal cord. A PARP-1 in- hibitor (PJ34) and autophagy inhibitor (3-MA) were administered with bupivacaine in pregnant mice. Parp-1flox/flox mice were crossed with Nes-Cre transgenic mice to obtain neuronal conditional knock- down mice. Then, LC3B and P62 staining were performed to evaluate autophagic flux in the spinal cords of pregnant wild-type (WT) and Parp-1-/- mice. We performed transmission electron microscopy (TEM) to evaluate autophagosomes. Results: The present study showed that oxidative stress-mediated DNA damage and neuronal injury were increased after bupivacaine treatment in the spinal cords of pregnant mice. Moreover, PARP-1 was significantly activated, and autophagic flux was disrupted. Further studies revealed that PARP-1 knockdown and autophagy inhibitors could alleviate bupivacaine-mediated neurotoxicity in pregnant mice. Conclusion: Bupivacaine may cause neuronal DNA damage and PARP-1 activation in pregnant mice. PARP-1 further obstructed autophagic flux and ultimately led to neurotoxicity.

In the current E-healthcare scenarios, medical institutions are used to encrypt the information and store it in an Electronic Health Record (EHR) system in order to ensure the privacy of medical information. To realize data sharing, a Public-key Encryption with Keyword Search (PEKS) scheme is indispensable, ensuring doctors search for medical information in the state of ciphertext. However, the traditional PEKS scheme cannot resist the keyword guessing quantum computing attacks, and its security depends on the confidentiality of the secret key. In addition, classical PEKS hand over the search process to a third party, affecting the search results’ accuracy. Therefore, we proposed a postquantum Public-key Searchable Encryption scheme on Blockchain (PPSEB) for E-healthcare scenarios. Firstly, we utilized a lattice-based cryptographic primitive to ensure the security of the search process and achieve forward security to avoid key leakage of medical information. Secondly, we introduced blockchain technology to solve the problem of third-party untrustworthiness in the search process. Finally, through security analysis, we prove the correctness and forward security of the solution in the E-healthcare scenarios, and the comprehensive performance evaluation demonstrates the efficiency of our scheme compared with other existing schemes.

It is of great significance to optimize the spatial matching of basic education facilities in rural areas and promote the equalization of urban and rural basic public services and the overall revitalization of rural areas. Based on the theory of spatial accessibility and spatial balance of supply and demand, this paper constructs the evaluation system of rural basic education facilities and layout rationality. In this study, we took 42 primary and secondary schools and 2089 rural areas with concentrated population in six township areas of Hancheng City as the research subjects. We used ArcGIS network analysis, population coupling model, and other methods, from the administrative scale and rural population concentration area scale for evaluation. The accessibility of basic education facilities and its coupling relationship with the spatial distribution of student population describe the spatial and geographical pattern of basic education facilities in rural areas. The results show that the accessibility of rural administrative scale and the spatial balance of supply and demand of population concentration area scale are associated with great problems, the differences between towns are obvious, and the overall level of the best performing towns is still low. On the scale of population concentration area, the overall coupling degree is too low, the “dislocation” distribution of educational facilities and student population is obvious, and the matching degree of the student population and school in different towns is significantly different, showing a more obvious “core-periphery” spatial structure characteristics centered on the eastern and southeast regions. The terrain characteristics of rural areas in Shaanxi province are prominent, and the accessibility of the road network is particularly significant. Therefore, optimizing the construction of rural roads and optimizing school layout according to local conditions will become an important solution to promote the balanced allocation of basic education resources in Shaanxi province.

Purchases of electric vehicles have been increasing in recent years. These vehicles differ from traditional fossil-fuel-based vehicles especially in the time consumed to keep them running. Electric-Vehicle-charging Service Providers (EVSPs) must arrange reasonable charging times for users in advance. Most EVSP services are based on third-party platforms, but reliance on third-party platforms creates a lack of security, leaving users vulnerable to attacks and user-privacy leakages. In this paper, we propose an anonymous blockchain-based system for charging-connected electric vehicles that eliminates third-party platforms through blockchain technology and the establishment of a multi-party security system between electric vehicles and EVSPs. In our proposed system, digital certificates are obtained by completing distributed Public Key Infrastructure (distributed-PKI) identity registration, with the user registration kept separate from the verification process, which eliminates dependence on the EVSP for information security. In the verification process, we adopt smart contracts to solve problems associated with centralized verification and opaque services. Furthermore, we utilize zero-knowledge proof and ring-signature superposition to realize completely anonymous verification, which ensures undeniability and unforgeability with no detriment to anonymity. The evaluation results show that the user anonymity, information authenticity, and system security of our system fulfill the necessary requirements.

The server logs play an essential role in website maintenance. When the Internet server is running, the service maintained may encounter various problems, and the logs generated by the server are the key data to locate the problems. However, the existing log storage systems are prone to a single point of failure, which may cause logs to be lost, and the problem cannot be rectified. Meanwhile, external attackers can tamper with logs to evade tracking, and the person in charge of an accident may also tamper with the log to evade responsibility. The advantages of blockchain, such as immutability, decentralization, and security, can effectively overcome these shortcomings. In this paper, we proposed a log data storage scheme based on blockchain and Interplanetary File System (IPFS). The lack of scalability of blockchain for storing large files is addressed by storing the log data stored in IPFS. Firstly, our model uses IPFS to store extensive file log data and combines blockchain technology to realize log data storage decentralization and difficulty to tamper. Secondly, to improve the query efficiency of log data, we propose two improved Merkle tree methods to provide fast queries of log data with a timestamp as query keywords. Finally, the experimental results show that the two methods have better log retrieval efficiency.

The research aimed to explore the biological role of p53 protein and long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in bupivacaine (bup)-induced neurotoxicity. Our work treated dorsal root ganglion (DRG) cells with bup, detected cell viability through CCK-8, apoptosis through TUNEL assays, DeoxyriboNucleic Acid (DNA) damage through γ-H2AX protein and comet assay, including p53 mRNA, protein and TUG1 expression through q-PCR and western blot, furthermore, cell viability and DNA damage were determined after the silencing of p53 and TUG1, biological information and TUG1 FISH combined with p53 protein immunofluorescence (IF) was performed to determine the cellular localization of these molecule.

Emergency responders must reach urgent cases within mandatory timeframes, regardless of weather conditions. However, flooding of transport networks can add critical minutes to travel times between dispatch and arrival. Here, we explicitly model the spatial coverage of all Ambulance Service and Fire and Rescue Service stations in England during flooding of varying severity under compliant response times. We show that even low-magnitude floods can lead to a reduction in national-level compliance with mandatory response times and this reduction can be even more dramatic in some urban agglomerations, making the effectiveness of the emergency response particularly sensitive to the expected impacts of future increases in extreme rainfall and flood risk. Underpinning this sensitivity are policies leading to the centralization of the Ambulance Service and the decentralization of the Fire and Rescue Service. The results provide opportunities to identify hotspots of vulnerability (such as care homes, sheltered accommodation, nurseries and schools) for optimizing the distribution of response stations and developing contingency plans for stranded sites.

Background Local anesthetic neurotoxicity is a common complication in clinical anesthesia, which can cause permanent nerve damage in severe cases. The T-type calcium channel is an important channel for regulating the excitability of neurons. Normally, extracellular calcium ions enter the cell through the T-type calcium channel to change the excitability of neurons. When the intracellular calcium is overloaded, it can cause cell damage. Aims To investigated the roles of T-type calcium channel in the SH-SY5Y cells injury induced by the bupivacaine. Methods The SH-SY5Y cell culture model was used to observe the effect of T-type calcium channel blocker NNC55-0396 on the neurotoxicity of bupivacaine hydrochloride by MTT methold,flow cytometry, Western blotting and other methods. Results The results show that NNC55-0396 can block the T-type calcium channel of SH-SY5Y cells, improve the decrease of cell viability caused by bupivacaine hydrochloride, reduce the level of intracellular calcium ion, reduce the expression of Cleavedcaspase-3, and reduce cell apoptosis. Conclusion The above results indicate that the T-type calcium channel is involved in the SH-SY5Y cell damage caused by bupivacaine hydrochloride, and blocking the T-type calcium channel can reduce the neurotoxicity of bupivacaine hydrochloride.

Manganese superoxide dismutase (SOD2) is a key enzyme to scavenge free radical superoxide in the mitochondrion. SOD2 deficiency leads to oxidative injury in cells. Bupivacaine, a local anesthetic commonly used in clinic, could induce neurotoxic injury via oxidative stress. The role and the mechanism of SOD2 regulation in bupivacaine-induced oxidative stress remains unclear. Here, bupivacaine was used to treat Sprague-Dawley rats with intrathecal injection and culture human neuroblastoma cells for developing vivo injury model and vitro injury model. The results showed that bupivacaine caused the over-production of mitochondrial reactive oxygen species (mtROS), the activation of C-Jun N-terminal kinase (JNK), and the elevation of SOD2 transcription. Decrease of mtROS with N-acetyl-L-cysteine attenuated the activation of JNK and the increase of SOD2 transcription. Inhibition of JNK signaling with a small interfering RNA (siRNA) or with sp600125 down-regulated the increase of SOD2 transcription. SOD2 gene knock-down exacerbated bupivacaine-induced mtROS generation and neurotoxic injury but had no effect on JNK phosphorylation. Mito-TEMPO (a mitochondria-targeted antioxidant) could protect neuron against bupivacaine-induced toxic injury. Collectively, our results confirm that mtROS stimulates the transcription of SOD2 via activating JNK signaling in bupivacaine-induced oxidative stress. Enhancing antioxidant ability of SOD2 might be crucial in combating bupivacaine-induced neurotoxic injury.

Background Both the clinical and preclinical studies have suggested embryonic or infant exposure to ketamine, a general anesthetic, pose a great threat to the developing brain. However, it remains unclear how ketamine may contribute to the brain dysfunctions. Methods A mouse model of prenatal exposure to ketamine was generated by i.m. injection and continuous i.p. infusion of pregnant mice. Open field test and elevated plus maze test were used to analyze the behavioral alterations induced by ketamine. Immunostaining by c-Fos was used to map the neuron activity. Chemogenetic modulation of the neurons was used to rescue the abnormal neuron activity and behaviors. Results Here we show that mice prenatally exposed to ketamine displayed anxiety-like behaviors during adulthood, but not during puberty. C-Fos immunostaining identified abnormal neuronal activity in Bed Nucleus of the Stria Terminalis, the silencing of which by chemogenetics restores the anxiety-like behaviors. Conclusions Taken together, these results demonstrate a circuitry mechanism of ketamine-induced anxiety-like behaviors.

In order to improve the inaccuracy of the GM(1,1) model in the prediction of ship traffic accidents caused by large data fluctuations, a weighted average weakening buffer operator is applied to the GM(1,1) residual error correction model to improve the prediction accuracy. This method is based on the modeling principle of the GM(1,1) residual error correction model. Firstly, GM(1,1) model is established based on the original data sequence to obtain the simulated value, predicted value, and residual tail sequence. Then, the residual tail sequence of the oscillation fluctuation is processed by positive value and weighted average weakening buffer operator, so as to establish the residual GM(1,1) model and correct the original prediction value with the residual prediction value; Finally, this method is applied to the prediction of British merchant shipping traffic accidents to verify its effectiveness. The results show that this method has high prediction accuracy in the short-term prediction of ship traffic accidents.

Bupivacaine, a local anesthetic widely used for regional anesthesia and pain management, has been reported to induce neuronal injury, especially DNA damage. Neurons employ different pathways to repair DNA damage. However, the mechanism underlying bupivacaine-mediated DNA damage repair is unclear. A rat neuronal injury model was established by intrathecal injection of (3%) bupivacaine. An in vitro neuronal injury model was generated by exposing SH-SY5Y cells to bupivacaine (1.5 mmol/L). Then, a cDNA plate array was used to identify the DNA repair genes after bupivacaine exposure. The results showed that xeroderma pigmentosum complementary group D (XPD) of the nuclear excision repair (NER) pathway was closely associated with the repair of DNA damage induced by bupivacaine. Subsequently, Western blot assay and immunohistochemistry indicated that the expression of the repair enzyme XPD was upregulated after DNA damage. Downregulation of XPD expression by a lentivirus aggravated the DNA damage induced by bupivacaine. In addition, phosphatidyl-3-kinase (PI3K)/AKT signaling in neurons was inhibited after exposure to bupivacaine. After PI3K/AKT signaling was inhibited, bupivacaine-mediated DNA damage was further aggravated, and the expression of XPD was further upregulated. However, knockdown of XPD aggravated bupivacaine-mediated neuronal injury but did not affect PI3K/AKT signaling. In conclusion, the repair enzyme XPD, which was partially regulated by PI3K/AKT signaling, responded to bupivacaine-mediated neuronal DNA damage. These results can be used as a reference for the treatment of bupivacaine-induced neurotoxicity.

BackgroundPostoperative delirium (POD) is a common complication after orthopedic surgery in elderly patients. The elderly may experience drastic changes in autonomic nervous system (ANS) activity and circadian rhythm disorders after surgery. Therefore, we intend to explore the relationship between postoperative long-term heart rate (HR) variability (HRV), as a measure of ANS activity and circadian rhythm, and occurrence of POD in elderly patients.MethodsThe study population of this cohort was elderly patients over 60 years of age who scheduled for orthopedic surgery under spinal anesthesia. Patients were screened for inclusion and exclusion criteria before surgery. Then, participants were invited to wear a Holter monitor on the first postoperative day to collect 24-h electrocardiographic (ECG) data. Parameters in the time domain [the standard deviation of the normal-to-normal (NN) intervals (SDNN), mean of the standard deviations of all the NN intervals for each 5-min segment of a 24-h HRV recording (SDNNI), and the root mean square of successive differences of the NN intervals (RMSSD)] and frequency domain [heart rate (HR), high frequency (HF), low frequency (LF), very low frequency (VLF), ultra low frequency (ULF), and total power (TP)] were calculated. Assessment of delirium was performed daily up to the seventh postoperative day using the Chinese version of the 3-Min Diagnostic Interview for CAM-defined Delirium (3D-CAM). The relationship between HRV and POD, as well as the association between HRV and duration of POD, was assessed.ResultsOf the 294 cases that finally completed the follow-up, 60 cases developed POD. Among the HRV parameters, SDNNI, VLF, and ULF were related to the occurrence of POD. After adjustment for potential confounders, the correlation between HRV indices and POD disappeared. Through stratified analysis, two significant negative correlations emerged: ULF in young-old participants and SDNNI, VLF, and ULF in male patients.ConclusionThe lower HRV parameters may be related to the occurrence of POD, and this correlation is more significant in young-old and male patients. ANS disorders and rhythm abnormalities reflected by HRV changes may represent a possible mechanism that promotes POD.

Fu, Z.; Ding, W., and Xu, S., 2020. Analysis of the effect of grid computing on cross-organizational coordination in marine supply chain. In: Yang, D.F. and Wang, H. (eds.), Recent Advances in Marine Geology and Environmental Oceanography. Journal of Coastal Research, Special Issue No. 108, pp. 258–261. Coconut Creek (Florida), ISSN 0749-0208.With the continuous warming of the process of economic and trade globalization, the production and operation activities and resource allocation behavior of a country or region are less and less restricted by national boundaries. The ocean has been further transformed from a transport hub for goods into a basic platform for international resource allocation. As an inevitable node of international economy and trade, the ocean occupies an increasing proportion of influential factors of international economic development in the supply-chain management mode year by year. The Internet can play an important role in the coordination of the marine supply chain, and the grid, a product of its Internet development, will also play an important role in the coordination of the marine supply chain. On the basis of its grid computing, cross-organizational coordination in the ocean supply chain is able to handle its complex business and financial analysis with difficulty. Grid computing will lead to collaboration across the ocean supply chain and ultimately to the best possible coordination of services.

Ji Li,1 Wenjing Guo,1 Wei Zhao,1 Xiang Wang,1 Wenmin Hu,1 Jie Zhou,2 Shiyuan Xu,1 Hongyi Lei1 1Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Hongyi Lei; Shiyuan Xu Department of AnesthesiologyZhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of ChinaTel/Fax +86-20-62782898Email lhy2012@smu.edu.cn; xsy998@smu.edu.cnBackground: Peritoneal dialysis catheter placement can be performed under general anesthesia, local anesthesia or subarachnoid anesthesia (SA). Recently, studies have reported the successful placement of peritoneal dialysis catheters using a transversus abdominis plane (TAP) block and rectus sheath (RS) block. This study compared the TAP + RS block with SA for patients undergoing peritoneal dialysis catheter placement.Methods: Sixty patients were randomly divided into two groups, with 30 receiving unilateral ultrasound-guided TAP + RS block anesthesia and 30 receiving SA. The demographic characteristics, anesthesia efficacy, indicators related to anesthesia or operation, hemodynamic index, postoperative pain numeric rating score (NRS), postoperative recovery indicators, complications related to anesthesia or surgery, and dosage of sedative or analgesic medication were analyzed.Results: Anesthesia operation time was significantly shorter in the TAP + RS block group than in the SA group (P< 0.001), while there was no significant difference in success rates (TAP + RS 93.33% [95% confidence interval, 95% CI, 83.9– 102.8%] vs SA 100.00% [95% CI, 100– 100%], P=0.472). Two patients in the TAP + RS group needed extra analgesia, although the dermatome pinprick sensation test gave negative results for all patients. Patients who received the TAP + RS block expressed significantly less pain on movement or at rest at 4 h and 8 h postoperative. Fewer patients needed rescue analgesia with tramadol in the postoperative period in the TAP + RS block group than in the SA group (P< 0.05). The intraoperative MAP was more stable (P< 0.05) in the TAP + RS group compared to the SA group.Conclusion: The TAP + RS block is a safe, effective method for use as the principal anesthesia technique in PD catheter placement. Compared to SA, it has the advantages of less influence on hemodynamics and a better postoperative analgesic effect.Keywords: TAP block, rectus sheath block, peritoneal dialysis catheter placement, local anesthesia, subarachnoid anesthesia

Background Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI. Methods In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated. Results The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues. Conclusions Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.

Bupivacaine has been widely used in clinical Anesthesia, but its neurotoxicity has been frequently reported, implicating cellular oxidative DNA damage as the major underlying mechanism. However, the mechanism underlying bupivacaine-induced oxidative DNA damage is unknown. We, thus, exposed SH-SY5Y cells to 1.5mM bupivacaine to induce neurotoxicity. Then, iTRAQ proteomic analysis was used to explore the repair of neuronal oxidative DNA damage. By analyzing the STRING version 11.0 database, the bioinformatics relationship between key repair enzymes was tracked. Subsequently, immunofluorescence co-localization and immunoprecipitation were used to investigate the interaction between key repair enzymes. The iTRAQ showed that Poly [ADP-ribose] polymerase 1 (PARP-1) from the base excision repair pathway participated closely in the repair of oxidative DNA damage induced by bupivacaine, and inhibition of PARP-1 expression significantly aggravated bupivacaine-induced DNA damage and apoptosis. Interestingly, this study showed that there were interactions and co-expression between PARP-1 and XPD (xeroderma pigmentosum D), another key protein of the nucleic acid excision repair pathway. After inhibiting XPD, PARP-1 expression was significantly reduced. However, simultaneous inhibition of both XPD and PARP-1 did not further increase DNA damage. It is concluded that PARP-1 may repair bupivacaine-induced oxidative DNA damage through XPD-mediated interactions.

Additional file 2: Supplementary Fig. 2. Raw images of HE staining in Fig. 4a.

Additional file 1: Supplementary Fig. 1. Uncropped blots for images shown throughout the paper.

Data about the feasibility and safety of thoracoscopic surgery under non-intubated anesthesia and regional block are limited. In this prospective study, 57 consecutive patients scheduled for thoracoscopic surgery were enrolled. Patients were sedated with dexmedetomidine and anesthetized with propofol and remifentanil. Ropivacaine was used for intercostal nerve and paravertebral block. Lidocaine was used for vagal block. The primary outcomes were mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and end-tidal carbon dioxide partial pressure (ETCO2) at T0 (pre-anesthesia), T1 (immediately after laryngeal mask/nasopharyngeal airway placement), T2 (immediately after skin incision), T3 (10 min after opening the chest), T4 (end of surgery), and T5 (immediately after laryngeal mask/nasopharyngeal airway removal). One patient required conversion to intubation, 15 developed intraoperative hypotension, and two had hypoxemia. MAP at T0 and T5 was higher than at T1-T4; MAP at T3 was lower (P

Background: The optimized procedures for local anesthetic (LA) delivery and resuscitation for LA systemic toxicity (LAST) have improved the safety of regional anesthesia. Lipid emulsion (LE) has been the valid treatment for LAST. However, adoption of these revised procedures in developing countries remains unknown.Methods: We conducted a 17-question survey to access the basic knowledge of LA delivery, the practice procedures for LAST resuscitation and an overall understanding of LE usage in both academic and non-academic hospitals of the Chinese Society of Anesthesiology.Results: A total of 250 hospitals completed the survey. Ropivacaine was the most preferred long-acting LA for regional anesthesia. Among the responders, 10 hospitals did not apply test-dosing before epidural anesthesia, including more non-academic than academic hospitals (7.1% versus 1.4%, P=0.0223). 77.5% (107/138) of academic hospitals and 69.6% (78/112) of non-academic hospitals had a protocol for LAST resuscitation. Only 28.2% of academic and 18.8% of non-academic hospitals stated LE preference for LAST. Furthermore, 17% (22/132) academic hospitals and 13% (12/89) non-academic hospitals chose the recommended epinephrine dosage based on the guideline of ARSA for LA-induced cardiac arrest. Significantly higher proportion (1.6 times more, 95% CI 1.082-3.991) of academic hospitals considered LE as the resuscitation method for LA-induced seizure than non-academic hospitals (44.9% versus 28.2%, P=0.0269). Finally, LE was available in only half of the hospitals which adopted its feasibility for LAST resuscitation.Conclusions: The survey revealed the poor practice procedures for regional anesthesia and non-standard use of LE for LAST resuscitation in China, especially among non-academic hospitals. Citation: Feng-Xian Li, Hua-Li Xu, Hui-Qun Chen, Hong-Yi Lei, Zhi-Jian You, Xu-Zhong Xu, et al. Local anesthetic delivery and resuscitation for systemic toxicity in China: a survey of 250 hospitals. J Anesth Perioper Med 2017; x: x-x. doi:10.24015/JAPM.2017.0021This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Inadvertent intraoperative hypothermia (core temperature

Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats.A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury.The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P.001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 μm, DN + Bup, 7.5 ± 0.3 μm, P.001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 μm). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P.05).Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin-induced DN model.

Evasion of carbon dioxide (CO2) and methane (CH4) in streams and rivers play a critical role in global carbon (C) cycle, offsetting the C uptake by terrestrial ecosystems. However, little is known about CO2 and CH4 dynamics in lowland coastal rivers profoundly modified by anthropogenic perturbations. Here, we report results from a long-term, large-scale study of CO2 and CH4 partial pressures (pCO2 and pCH4) and evasion rates in the Shanghai river network. The spatiotemporal variability of pCO2 and pCH4 were examined along a land-use gradient and the annual CO2 and CH4 evasion were estimated to assess its role in regional C budget. During the study period (August 2009 – October 2011), the overall mean pCO2 and median pCH4 from 87 surveyed rivers were 5846±2773 μatm and 241 μatm, respectively. Internal metabolic CO2 production and DIC input via upstream runoff were the major sources sustaining the widespread CO2 supersaturation, coupling pCO2 to biogeochemical and hydrological controls, respectively. While CH4 was oversaturated throughout the river network, CH4 hotpots were concentrated in the small urban rivers and highly discharge-dependent. The Shanghai river network played a disproportionately important role in regional C budget, offsetting up to 40% of the regional terrestrial net ecosystem production (NEP) and 10% of net C uptake in the river-dominated East China Sea fueled by anthropogenic nutrient input. Given the rapid urbanization in global coastal areas, more research is needed to quantify the role of lowland coastal rivers as a major landscape C source in global C budget.

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury.