A preliminary study on the spasticity reduction of quadriceps after selective dorsal rhizotomy in pediatric cases of spastic cerebral palsy.

OBJECTIVE: This study aimed to evaluate the potential alleviation of quadriceps spasticity in children diagnosed with spastic cerebral palsy (CP) following selective dorsal rhizotomy (SDR). METHODS: A retrospective study was conducted on children suffering from spastic CP who underwent SDR at the Department of Neurosurgery, Shanghai Children's Hospital, from July 2018 to September 2020. Inclusion criteria comprised children exhibiting quadriceps spasticity exceeding modified Ashworth Scale grade 2. Muscle tone and motor function were assessed before the operation, at short-term follow-up and at the last follow-up after SDR. Additionally, intraoperative neurophysiological monitoring data were reviewed. RESULTS: The study comprised 20 eligible cases, where, prior to surgery, 35 quadriceps muscles exhibited spasticity exceeding modified Ashworth Scale grade 2. Following short-term and mid-term follow-up, specifically an average duration of 11 ± 2 days and 1511 ± 210 days after SDR, it was observed that muscle tension in adductors, hamstrings, gastrocnemius, and soleus decreased significantly. This reduction was accompanied by a decrease in quadriceps muscle tone in 24 out of 35 muscles (68.6%). Furthermore, the study found that intraoperative electrophysiological parameters can predict postoperative spasticity relief in the quadriceps. The triggered electromyographic (EMG) output of the transected sensory root/rootlets after single-pulse stimulation revealed that the higher the EMG amplitudes in quadriceps, the greater the likelihood of postoperative decrease in quadriceps muscle tension. CONCLUSIONS: SDR demonstrates the potential to reduce muscle spasticity in lower extremities in children diagnosed with CP, including a notable impact on quadriceps spasticity even they are not targeted in SDR. The utilization of intraoperative neurophysiological monitoring data enhances the predictability of quadriceps spasticity reduction following SDR.

The discrepancy in triggered electromyography responses between fatty filum and normal filum terminale.

BACKGROUND: Functional role of filum terminale (FT) was not well studied though it contains structure basis for nerve impulse conduction. We aimed to explore the possible functions of the FT from the perspective of triggered electromyography (EMG) during surgery. METHODS: We retrospectively reviewed intraoperative neurophysiological monitoring data from pediatric patients who underwent intradural surgeries at the lumbar level in Shanghai Children's. Hospital from January 2018 to March 2023. Altogether 168 cases with complete intraoperative neurophysiological recordings of the FT were selected for further analysis. Triggered EMG recordings of the filum originated from two main types of surgeries: selective dorsal rhizotomy (SDR) and fatty filum transection. RESULTS: 96 cases underwent SDR and 72 cases underwent fatty filum transection. Electrical stimulation of the FT with fatty infiltration did not elicit electromyographic activity in the monitored muscles with the maximum stimulus intensity of 4.0 mA, while the average threshold for FT with normal appearance was 0.68 mA, and 89 out of 91 FT could elicit electromyographic responses in monitored channels. The threshold ratio of filum to motor nerve roots at the same surgical segment was significantly higher in patients with fatty filum, and a cut-off point of 21.03 yielded an area under curve of 0.943, with 100% sensitivity and 85.71% specificity. CONCLUSION: Filum with normal appearance can elicit electromyographic activity in the lower limbs/anal sphincter similar to the performance of the cauda equina nerve roots. The threshold of fatty filum is different from that of normal appearing FT. Triggered EMG plays an important role in untethering surgeries.

Nrf2 attenuates oxidative stress to mediate the protective effect of ciprofol against cerebral ischemia-reperfusion injury.

Neuroinflammation and oxidative stress damage are involved in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Ferroptosis emerged as a new player in the regulation of lipid peroxidation processes. This study aimed at exploring the potential involvement of ciprofol on ferroptosis-associated CIRI and subsequent neurological deficits in the mouse model of transient cerebral ischemia and reperfusion. Cerebral ischemia was built in male C57BL/6 J wild-type (WT) and Nrf2-knockout (Nrf2 KO) mice in the manner of middle cerebral artery occlusion (MCAO) followed by reperfusion. Ciprofol improved autonomic behavior, alleviated reactive oxygen species output and ferroptosis-induced neuronal death by nucleus transportation of NFE2 like BZIP transcription factor 2 (Nrf2) and the promotion of heme oxygenase 1 (Ho-1), solute carrier family 7 member 11 (SLC7A11/xCT), and glutathione peroxidase 4 (GPX4). Additionally, ciprofol improved neurological scores and reduced infarct volume, brain water content, and necrotic neurons. Cerebral blood flow in MCAO-treated mice was also improved. Furthermore, absence of Nrf2 abrogated the neuroprotective actions of ciprofol on antioxidant capacity and sensitized neurons to oxidative stress damage. In vitro, the primary-cultured cortical neurons from mice were pre-treated with oxygen-glucose deprivation/reperfusion (OGD/R), followed by ciprofol administration. Ciprofol effectively reversed OGD/R-induced ferroptosis and accelerated transcription of GPX4 and xCT. In conclusion, we investigated the ciprofol-induced inhibition effect of ferroptosis-sheltered neurons from lipid preoxidation in the pathogenesis of CIRI via Nrf2-xCT-GPX4 signaling pathway.

TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy.

BACKGROUND: Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. METHODS: SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. RESULTS: Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. CONCLUSION: TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.

Impact of Transcutaneous Electrical Acupoint Stimulation on Delayed Neurocognitive Recovery in Elderly Patients Following Bronchoscopy.

Background: Postoperative cognitive dysfunction (POCD) is a significant neurological issue after surgery, linked to increased mortality, extended hospital stays, higher costs, and workforce dropout. However, effective prevention methods for POCD remain elusive. Objective: This study aims to investigate the impact of transcutaneous electrical acupoint stimulation (TEAS) on the cognitive function of elderly patients after bronchoscopy. Design: The research team conducted a double-blind, randomized, controlled clinical trial. Setting: The study was conducted at a university hospital in Wenzhou, China. Participants: The study involved 80 patients who underwent bronchoscopy between December 2019 and September 2020. Intervention: The participants were randomly assigned to two groups, each with 40 participants: the intervention and control groups. The intervention group received Transcutaneous Electrical Acupoint Stimulation (TEAS) for 30 minutes before anesthesia, while the control group had electrodes applied but did not receive stimulation. Outcome Measures: Seven neuropsychological tests were administered before the operation and one day afterwards. Participants were also assessed via telephone after 7 days and one-month post-operation. Results: The TEAS group exhibited a significant reduction in the incidence of delayed neurocognitive recovery (DNR) compared to the control group on the 7th-day post-operation, although no such difference was observed at 1 day and 30 days post-operation. Conclusion: TEAS demonstrated positive effects in preventing cognitive decline in elderly patients undergoing bronchoscopy.

Analysis of preoperative sleep quality and related influencing factors in cancer patients.

PURPOSE: The sleep disturbance in cancer patients is more prevalent, and it significantly affects these patients' recovery after the operation. However, the clinical characteristics regarding sleep quality are scarce. This study aimed to evaluate the quality of preoperative sleep quality and its risk factors in different cancer patients requiring elective surgery. PATIENTS AND METHODS: Cancer patients who were scheduled for elective surgery were selected. The demographic data, basic preoperative diseases, and factors related to the preoperative hospital environment were also recorded. Self-made questionnaires (such as gender, age, and personal history), and the Anxiety Self-Assessment Scale were used to assess the patient's underlying condition. The modified Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the preoperative sleep status. RESULTS: A total of 297 patients completed the investigation. The incidence of preoperative sleep disturbance in cancer patients was 47.8%. Multiple logistic regression showed that patients with PSQI ≥ 7 were associated with females (odds ratios [95% confidence intervals]): 1.815 [1.031-3.193], p = 0.039), and the ward space was confined (3.127 [1.016-9.625], p = 0.047), which increased the possibility of sleep disturbance in cancer patients. Meanwhile, increased anxiety levels (1.323 [1.261-1.439], p < 0.001) significantly increased the likelihood of sleep disorders in cancer patients. CONCLUSION: 47.8% of sleep disturbance in cancer patients before surgery. Female patients, preoperative anxiety, and confined ward environment were independent risk factors of subjective sleep disturbance.

Maternal immune activation alters visual acuity and retinogeniculate axon pruning in offspring mice.

Individuals with autism spectrum disorder (ASD) have been found to have a variety of sensory processing deficits. Here we report that maternal immune activation, a known factor for ASD, alters visual acuity in the offspring mice. By intraperitoneally injecting polyinosinic-polycytidylic acid (polyI:C) to induce maternal immune activation during embryonic days 10 to 14, we found that polyI:C treatment impairs visual acuity in young adult offspring mice as examined by their optomotor responses. Concurrently, polyI:C treatment suppresses retinogeniculate axon elimination, resulting in a high fraction of weak optical fibers innervating the relay neurons in the visual thalamus. The results link in-utero maternal inflammation to defective optical fiber pruning and arrested developmental strengthening of single optic fibers which may underlie impaired visual acuity.

Whether the newly modified rhizotomy protocol is applicable to guide single-level approach SDR to treat spastic quadriplegia and diplegia in pediatric patients with cerebral palsy?

PURPOSE: Our aim was to test whether the newly modified rhizotomy protocol which could be effectively used to guide single-level approach selective dorsal rhizotomy (SL-SDR) to treat spastic hemiplegic cases by mainly releasing those spastic muscles (target muscles) marked pre-operatively in their lower limbs was still applicable in spastic quadriplegic or diplegic cerebral palsy (CP) cases in pediatric population. METHODS: In the current study, we retrospectively conducted a cohort review of cases younger than 14 years of age diagnosed with spastic quadriplegic or diplegic CP who undergone our modified protocol-guided SL-SDR in the Department of Neurosurgery, Children's Hospital of Shanghai since July 2016 to November 2017 with at least 12 months post-op intensive rehabilitation program (pre-op GMFCS level-based). Clinical data including demographics, intra-operative EMG responses interpretation, and relevant assessment of included cases were taken from the database. Inclusion and exclusion criteria were set for the selection of patients in the current study. Muscle tone (modified Ashworth scale) and strength of those spastic muscles (muscle strength grading scale), range of motion (ROM) of those joints involved, the level of Gross Motor Function Classification System (GMFCS), and Gross Motor Function Measure 66 items (GMFM-66) score of those cases were our focus. RESULTS: A total of 86 eligible cases were included in our study (62 boys). Among these patients, 61.6% were quadriplegic. Pre-operatively, almost 2/3 of our cases were with GMFCS levels II and III. Mean age at the time of surgery in these cases was 6.2 (3.5-12) years. Pre-op assessment marked 582 target muscles in these patients. Numbers of nerve rootlets tested during SDR procedure were between 52 and 84 across our cases, with a mean of 66.5 ± 6.7/case. Among those tested (5721 in 86 cases), 47.9% (2740) were identified as lower limb-related sensory rootlets. Our protocol successfully differentiated sensory rootlets which were considered to be associated with spasticity of target muscles across all our 86 cases (ranged from 3 to 21). Based on our protocol, 871 dorsal nerve rootlets were sectioned 50%, and 78 were cut 75%. Muscle tone of those target muscles reduced significantly right after SL-SDR procedure (3 weeks post- vs. pre-op, 1.7 ± 0.5 vs. 2.6 ± 0.7). After an intensive rehabilitation program for 19.9 ± 6.0 months, muscle tone continued to decrease to 1.4 ± 0.5. With the reduction of muscle tone, strength of those target muscles in our cases improved dramatically with statistical significance achieved (3.9 ± 1.0 at the time of last follow-up vs. 3.3 ± 0.8 pre-op), and as well as ROM. Increase in GMFCS level and GMFM-66 score was observed at the time of last follow-up with a mean of 0.4 ± 0.6 and 6.1 ± 3.2, respectively, when compared with that at pre-op. In 81 cases with their pre-op GMFCS levels II to V, 27 (33.3%) presented improvement with regard to GMFCS level upgrade, among which 4 (4.9%) even upgraded over 2 levels. Better results with regard to upgrading in level of GMFCS were observed in cases with pre-op levels II and III when compared with those with levels IV and V (24/57 vs. 3/24). Upgrading percentage in cases younger than 6 years at surgery was significantly greater than in those older (23/56 vs. 4/25). Cases with their pre-op GMFM-66 score ≥ 50 had greater score increase of GMFM-66 when compared with those less (7.1 ± 3.4 vs. 5.1 ± 2.8). In the meanwhile, better score improvement was revealed in cases when SDR performed at younger age (6.9 ± 3.3 in case ≤ 6 years vs. 4.7 ± 2.7 in case > 6 years). No permanent surgery-related complications were recorded in the current study. CONCLUSION: SL-SDR when guided by our newly modified rhizotomy protocol was still feasible to treat pediatric CP cases with spastic quadriplegia and diplegia. Cases in this condition could benefit from such a procedure when followed by our intensive rehabilitation program with regard to their motor function.

Electroacupuncture Attenuates CFA-Induced Inflammatory Pain by Regulating CaMKII.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase that is ubiquitously distributed in the central and peripheral nervous systems. Moreover, its phosphorylated protein (P-CaMKII) is involved in memory, mood, and pain regulation in the anterior cingulate cortex (ACC). Electroacupuncture (EA) is a traditional Chinese therapeutic technique that can effectively treat chronic inflammatory pain. However, the CaMKII-GluA1 role in EA analgesia in the ACC remains unclear. This study investigated the role of P-CaMKII and P-GluA1 in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). There were increased P-CaMKII and P-GluA1 levels in the ACC. We found that intracerebroventricular injection of KN93, a CaMKII inhibitor, as well as EA stimulation, attenuated complete Freund's adjuvant-induced pain behavior. Further, EA increased pCaMKII-PICK1 complex (abbreviated as C-P complex) levels. Our findings demonstrate that EA inhibits inflammatory pain by inhibiting CaMKII-GluA1 phosphorylation. P-CaMKII is involved in EA analgesia as the pCaMKII-PICK1 complex.

Spinal miR-34a regulates inflammatory pain by targeting SIRT1 in complete Freund's adjuvant mice.

Sirtuin1 (SIRT1), which is regulated by microRNA-34a (miR-34a), can modulate pathophysiology processes, including nonalcoholic fatty liver disease and intestinal ischemia/reperfusion injury. We previously reported that SIRT1, an NAD+-dependent deacetylase, plays a vital role in the development of neuropathic pain. However, the role of miR-34a/SIRT1 in complete Freund's adjuvant (CFA)-induced inflammatory pain remains unclear. In the present study, we examined miR-34a and SIRT1 in CFA mice. MiR-34a levels increased, while SIRT1 decreased in the spinal cord. Inhibiting miR-34a by intrathecal injection of miR-34a antagomir attenuated CFA-induced pain behavior. Moreover, miR-34a antagomir inhibited the CFA-induced SIRT1 decrease in the spinal cord. Furthermore, the analgesic effect of miR-34a antagomir was abrogated by the SIRT1 inhibitor EX-527. Our data provide support that the underlying mechanisms of miR-34a in promoting inflammatory pain may involve negative regulation of SIRT1.

PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and Amplifies Sepsis-Induced Acute Lung Injury.

Sepsis is a systemic inflammatory reaction caused by infection. Multiple organ failure ultimately leads to high morbidity and mortality. Unfortunately, therapies against these responses have been unsuccessful due to the insufficient underlying pathophysiological evidence. Protein interacting with C-kinase 1 (PICK1) has received considerable attention because of its important physiological functions in many tissues. However, its role in sepsis-induced acute lung injury (ALI) is unclear. In this study, we used cecal ligation and puncture (CLP) to establish a septic model and found that decreased microtubule-associated protein-1light chain 3 (LC3)-II/LC3-I in PICK1-/- septic mice was caused by autophagy dysfunction. Consistently, the transmission electron microscopy (TEM) of bone marrow-derived macrophages (BMDMs) from PICK1-/- mice showed the accumulation of autophagosomes as well. However, more serious damage was caused by PICK1 deficiency indicating that the disrupted autophagic flux was harmful to sepsis-induced ALI. We also observed that it was the impaired lysosomal function that mediated autophagic flux blockade, and the autophagy progress was relevant to PI3K-Akt-mTOR pathway. These findings will aid in the potential development of PICK1 with novel evidence of autophagy in sepsis treatment and prevention.

The Effect of Transcutaneous Electrical Acupoint Stimulation on Inflammatory Response in Patients Undergoing Limb Ischemia-Reperfusion.

Reperfusion after tourniquet use can induce inflammation and cause remote organ injury. We evaluated the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) on inflammatory mediators and lung function in patients receiving lower limb tourniquets. Forty patients undergoing unilateral lower extremity surgery with tourniquet were randomly assigned to two groups: the TEAS group and ischemia-reperfusion (I/R) group. The C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8 (CXCL8), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and arterial blood gas analysis were measured preoperatively and 6 h after tourniquet removal. The levels of CXCL8, IL-1, IL-6, TNF-α, and CCL2 were significantly increased compared to baseline values in both groups, but the increase was significantly smaller in the TEAS group. In the TEAS group, the partial pressure of oxygen and arterial-alveolar oxygen tension ratio were significantly decreased, and the alveolar-arterial oxygen tension difference and respiratory index were significantly increased, compared to those in the I/R group at 6 h after reperfusion. In conclusion, TEAS diminished the upregulation of proinflammatory factors in response to lower limb ischemia-reperfusion and improved pulmonary gas exchange.

Prevention of propofol injection-related pain using pretreatment transcutaneous electrical acupoint stimulation

Background/aim: This study aimed to study the effect of pretreatment transcutaneous electrical acupoint stimulation (TEAS) in preventing propofol injection-related pain. Materials and methods: A total of 360 patients who were to undergo elective hysteroscopy surgery were randomly divided into the following three groups of 120 patients each: control (Group C), sham TEAS (Group F), and TEAS (Group T). Patients in Group C did not undergo any treatment before surgery; 30 min before the induction of anesthesia, patients in Groups F and T underwent electrical stimulation of the bilateral LI4-PC6 acupoint. Patients in Group F were subjected to 'feeling flow', while those in Group T were subjected to 'tolerance flow.' The stimulation frequency was 2/100 Hz and the duration of stimulation was 30 min. After the induction of anesthesia, propofol injection-related pain scores, hemodynamic parameters, and adverse reactions were recorded. Results: Of the 360 patients, 324 completed the study. There were significant differences among the groups in terms of the incidence of moderate-to-severe pain. In terms of the four-point scaling method, the end of the radial vein, the cubital vein, and the 'back of the hand' vein differed significantly among the three groups (P = 0.05). Finally, using a numerical rating scale, a significant difference was observed among the three groups in terms of the pain scores in the different veins. Conclusions: Pretreatment TEAS effectively reduces the incidence and severity of propofol injection-related pain, the incidence of postoperative nausea and vomiting, and patient postoperative pain scores.

Geometry-Based Distributed Spatial Skyline Queries in Wireless Sensor Networks.

Algorithms for skyline querying based on wireless sensor networks (WSNs) have been widely used in the field of environmental monitoring. Because of the multi-dimensional nature of the problem of monitoring spatial position, traditional skyline query strategies cause enormous computational costs and energy consumption. To ensure the efficient use of sensor energy, a geometry-based distributed spatial query strategy (GDSSky) is proposed in this paper. Firstly, the paper presents a geometry-based region partition strategy. It uses the skyline area reduction method based on the convex hull vertices, to quickly query the spatial skyline data related to a specific query area, and proposes a regional partition strategy based on the triangulation method, to implement distributed queries in each sub-region and reduce the comparison times between nodes. Secondly, a sub-region clustering strategy is designed to group the data inside into clusters for parallel queries that can save time. Finally, the paper presents a distributed query strategy based on the data node tree to traverse all adjacent sensors' monitoring locations. It conducts spatial skyline queries for spatial skyline data that have been obtained and not found respectively, so as to realize the parallel queries. A large number of simulation results shows that GDSSky can quickly return the places which are nearer to query locations and have larger pollution capacity, and significantly reduce the WSN energy consumption.

Loss of ICA69 potentiates long-lasting hyperalgesia after subcutaneous formalin injection into the mouse hindpaw.

Islet-cell autoantigen 69 kDa (ICA69) plays an important role in many diseases and physiological activities by forming heteromeric complexes with protein interacts with C-kinase 1 (PICK1). PICK1 is critical for inflammatory pain hypersensitivity by regulating trafficking of AMPA receptor subunit GluA2 in spinal neurons. However, the role of ICA69 in inflammatory pain has not yet been investigated. Here we reported that expression of PICK1 in spinal cord was reduced largely in ICA69 knockout mice. The pain hypersensitivity was enhanced in the second phase 7 days after formalin administration. Meanwhile, increased Ser880 phosphorylation in GluA2 and decreased surface GluA2 were concordant with the pain. Furthermore, the number of activated microglia in spinal dorsal horn increased in line with pain hypersensitivity. Together, ICA69 deficiency promoted the internalization of GluA2 and FML-induced long-lasting pain hypersensitivity. In addition, microglia activation might be an important factor in the development of the pain hypersensitivity.

Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery.

OBJECTIVE: Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. METHODS: Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by PCA pump. RESULTS: Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. CONCLUSION: Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

[Adenosine Al Receptor Mediated Neuroprotection of Shenmai Injection on Rat Cerebral Ischemia/Reperfusion Injury: an Experimental Study].

OBJECTIVE: To observe whether adenosine Al receptor (Al R) mediated neuroprotection of Shenmai Injection (SI) on rat cerebral ischemia/reperfusion (I/R) injury. METHODS: The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO). Totally 60 successfully modeled rats was divided into 5 groups according to randomized block principle, i.e., the model group, the SI group, the SI + AlR antagonist (1,3-dipropyl-8-cyclopentylxanthine, DPCPX) group, the AlR antagonist control group, and the dimethyl sulfoxide (DMSO) control group, 12 in each group. Besides, a sham-operation group was set up (n =12). SI at 15 mL/kg was peritoneally injected to mice in the SI group immediately after cerebral I/R. Equal volume of normal saline was injected to mice in the model group and the sham-operation group. DPCPX at 1 mg/mL was peritoneally injected to mice in the Al R antagonist control group 30 min before peritoneal injecting SI. DPCPX at 1 mg/kg and DMSO at 1 mL/kg were peritoneally injected to mice in the AlR antagonist control group and the DMSO control group 30 min immediately before cerebral I/R. Rats' neurobehavioral scores were assessed after 24 h reperfusion. The volume of cerebral infarction and Bcl-2 protein expression of cerebral infarction penumbra were also detected. Results Compared with the sham-operation group, neurobehavioral scores, the volume of cerebral infarction, and Bcl-2 protein expression increased (all P <0. 05). Compared with the model group, neurobehavioral scores and the volume of cerebral infarction obviously decreased, but Bcl-2 protein expression increased in the SI group (all P <0. 05). Compared with the SI group, neurobehavioral scores increased, the volume of cerebral infarction was obviously enlarged, and Bcl-2 protein expression was obviously reduced in the A1R antagonist control group (all P <0. 05). CONCLUSIONS: SI's neurobehavioral scores could be partially reversed in the Al R antagonist control group, the volume of cerebral infarction and Bcl-2 protein expression improved. AlR might possibly meditate neuroprotection of SI on MACO mire

An enterprise composite blockchain construction method for business environment.

In order to foster a modern economic system and facilitate high-quality economic development, it is crucial to establish a conducive business environment. Undoubtedly, the evaluation of the business environment for enterprises constitutes a prominent area of research. Nevertheless, ensuring the authenticity and security of the raw data sources provided by participating enterprises poses a challenge, thereby compromising the accuracy of the evaluation. To tackle this issue, an enterprise composite blockchain construction method for business environment is proposed in this paper, which stores the raw data of enterprises by the means of hybrid on-chain and off-chain. Initially, the enhanced hash function SHA256 is introduced to encrypt the raw data of enterprises. The encrypted data is subsequently stored in an off-chain Level DB database, which is based on non-volatile memory. This approach effectively alleviates the burden on communication and storage. Secondly, a composite storage strategy on-chain is adopted: the key values from the Level DB are stored in the DAG-based Conflux public blockchain, while the enterprise state data is stored in the consortium blockchain, so as to provide trusted evidence of business environment evaluation data. Finally, it is demonstrated through a large number of experimental comparisons that the enterprise composite blockchain construction method proposed in this paper exhibits better read and write performance, lower storage efficiency and storage overhead, and outperforms both the before-improved Level DB database and existing blockchain storage models.

Multi-level index construction method based on master-slave blockchains.

Master-slave blockchain is a novel information processing technology that is domain-oriented and uses efficient cryptography principles for trustworthy communication and storage of big data. Existing indexing methods primarily target the creation of a single-structured blockchain, resulting in extensive time and memory requirements. As the scale of domain data continues to grow exponentially, master-slave blockchain systems face increasingly severe challenges with regards to low query efficiency and extended traceback times. To address these issues, this paper propose a multi-level index construction method for the master-slave blockchain (MLI). Firstly, MLI introduces a weight matrix and partitions the entire master-slave blockchain based on the master chain structure, the weight of each partition is assigned. Secondly, for the master blockchain in each partition, a master chain index construction method based on jump consistent hash (JHMI) is proposed, which takes the key value of the nodes and the number of index slots as input and outputs the master chain index. Finally, a bloom filter is introduced to improve the column-based selection function and build a secondary composite index on the subordinate blockchain corresponding to each master block. Experimental results on three constraint conditions and two types of datasets demonstrate that the proposed method reduce the index construction time by an average of 9.28%, improve the query efficiency by 12.07%, and reduce the memory overhead by 24.4%.

Electroacupuncture promotes macrophage/microglial M2 polarization and suppresses inflammatory pain through AMPK.

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.