Influence of Transverse Abdominis Plane Block on Intraoperative Diaphragmatic and Respiratory Functions in Patients Receiving Laparoscopic Colorectal Surgery.

Background: The positive roles of deep muscle relaxation in abdominal surgeries and transversus abdominis plane block (TAPB) in the postoperative analgesia. This study aimed to discuss the effects of TAPB on abdominal muscle relaxation, the intraoperative diaphragmatic, and the respiratory functions. Methods: The patients were randomly divided into the TAPB group who received single-shot TAPB bilaterally (n=30), and the control group who did not receive TAPB (n=30). Both groups keep the same steps for other procedures in the surgeries and anesthesia. Four time points for monitoring were defined: The moment when pneumoperitoneum pressure stabilized following endotracheal intubation and anesthetic induction (T0), appearance of the first incisure in the pressure-volume (P-V) loop (T1), appearance of the second incisure in the P-V loop (T2), and the moment with single stimulation (SS) =20% (T3). Primary observation parameters were SS1 measured by muscle relaxation monitoring at T1, and SS2 at T2. Secondary observation parameters included surgeon's satisfaction with surgical field and respiratory dynamics at the four time points. Results: The two groups were comparable in age, gender, BMI, ASA grade, and operation time. The TAPB group had a dramatic reduction in the total dose of intraoperative sufentanil (0.73±0.21 ug/kg) compared with the control group (0.87±0.18 ug/kg) (P=0.023); Other use of drug did not differ between the two groups. The two groups did not differ significantly in SS at either T1 (SS1) or T2 (SS2). In either group, surgeon's satisfaction with surgical field at T1 and T2 decreased dramatically compared with T0 and T3 (all P<0.05). At each time point, the respiratory dynamics and the surgeon's satisfaction with surgical field did not differ significantly between the two groups. Conclusion: TAPB reduced the use of intraoperative analgesics without altering the degree of abdominal relaxation, or affecting surgeon's satisfaction with surgical field in the patients receiving laparoscopic colorectal surgery.

A method to design a fast chaotic oscillator using CCTA.

This article introduces a novel method for designing a fast chaotic oscillator using a CCTA (Current Conveyor Transconductance Amplifier) based on Chua's circuit. The proposed method uses innovative configurations and advanced simulation techniques to overcome challenges in high-speed operation, nonlinear dynamics, and Analog Building Block (ABB) selection. The design begins with nonlinear negative resistance, essential for Chua's diode characteristics, including two negative resistances, NR1 and NR2. The circuit integrates one CCTA block, two grounded capacitors, two fixed resistors, one inductor, and one potentiometer. It is simulated using PSPICE with IC (Integrated Circuit) macro-models and 180nm CMOS (Complementary Metal Oxide Semiconductor) technology. Various chaotic waveforms and attractors are produced, validating the theoretical and mathematical predictions. By varying the resistance values (1450Ω, 1650Ω, 1800Ω, 1950Ω), the circuit exhibits different chaotic behaviors, such as large limit cycles, double-scroll attractors, Rossler-type attractors, and I-periodic attractors. FFT (Fast Fourier Transform) analysis confirms the highest dominant operating frequency of 37.5MHz. A Monte Carlo simulation with 100 runs shows maximum voltage variations in the chaotic waveforms of 5.21 % and 4.61 % across the capacitors, demonstrating robustness and reliability. This design offers significant advancements in implementing high-frequency chaotic oscillators, with potential applications in various fields requiring chaotic signal generation.•A novel design of Chua's diode and Chua's chaotic oscillator using only one CCTA block is presented in this paper.•The proposed chaotic oscillator achieves the highest operating frequency of 37.5MHz.•The proposed circuit is simulated using commercially available ICs (MAX435 and AD844) and CMOS 180nm technology in PSPICE to confirm its workability.

Improved automatic segmentation of brain metastasis gross tumor volume in computed tomography images for radiotherapy: a position attention module for U-Net architecture.

Background: Brain metastases present significant challenges in radiotherapy due to the need for precise tumor delineation. Traditional methods often lack the efficiency and accuracy required for optimal treatment planning. This paper proposes an improved U-Net model that uses a position attention module (PAM) for automated segmentation of gross tumor volumes (GTVs) in computed tomography (CT) simulation images of patients with brain metastases to improve the efficiency and accuracy of radiotherapy planning and segmentation. Methods: We retrospectively collected CT simulation imaging datasets of patients with brain metastases from two centers, which were designated as the training and external validation datasets. The U-Net architecture was enhanced by incorporating a PAM into the transition layer, which improved the automated segmentation capability of the U-Net model. With cross-entropy loss employed as the loss function, the samples from the training dataset underwent training. The model's segmentation performance on the external validation dataset was assessed using metrics including the Dice similarity coefficient (DSC), intersection over union (IoU), accuracy, sensitivity, specificity, Matthews correlation coefficient (MCC), and Hausdorff distance (HD). Results: The proposed automated segmentation model demonstrated promising performance on the external validation dataset, achieving a DSC of 0.753±0.172. In terms of evaluation metrics (including the DSC, IoU, accuracy, sensitivity, MCC, and HD), the model outperformed the standard U-Net, which had a DSC of 0.691±0.142. The proposed model produced segmentation results that were closer to the ground truth and could reveal more detailed features of brain metastases. Conclusions: The PAM-improved U-Net model offers considerable advantages in the automated segmentation of the GTV in CT simulation images for patients with brain metastases. Its superior performance in comparison with the standard U-Net model supports its potential for streamlining and improving the accuracy of radiotherapy. With its ability to produce segmentation results consistent with the ground truth, the proposed model holds promise for clinical adoption and provides a reference for radiation oncologists to make more informed GTV segmentation decisions.

Sjogren's Antibodies and Neonatal Lupus: A Scoping Review.

Sjogren's syndrome (SS) is an autoimmune disease characterized by inflammation of exocrine glands. The disorder predominantly affects middle-aged women. Autoantibodies, including anti-SS-A/Ro and anti-SS-B/La antibodies, are present in most cases of SS. These antibodies can cross the placenta and likely play a role in pregnancy complications as well as the development of neonatal lupus, resulting in congenital heart block (CHB). It is essential to monitor the fetus for CHB during pregnancy. In particular, screening with echocardiography and monitoring heart rate at home are recommended practices. Regarding medical management, hydroxychloroquine and glucocorticoids have shown promise in reducing cardiac manifestations, but further research is needed to elucidate their longer term efficacy and safety. This scoping review analyzes literature from 2001 to 2024, focusing on pregnancy outcomes among women with SS, clinical manifestations of neonatal lupus, the role of anti-SS-A/Ro and anti-SS-B/La antibodies in the development of neonatal lupus and CHB, and emphasizes the need for future research efforts to refine treatment protocols and enhance clinical care strategies for pregnant women with SS.

Block copolymer micelles as ocular drug delivery systems.

Block copolymer micelles, formed by the self-assembly of amphiphilic polymers, address formulation challenges, such as poor drug solubility and permeability. These micelles offer advantages including a smaller size, easier preparation, sterilization, and superior solubilization, compared with other nanocarriers. Preclinical studies have shown promising results, advancing them toward clinical trials. Their mucoadhesive properties enhance and prolong contact with the ocular surface, and their small size allows deeper penetration through tissues, such as the cornea. Additionally, copolymeric micelles improve the solubility and stability of hydrophobic drugs, sustain drug release, and allow for surface modifications to enhance biocompatibility. Despite these benefits, long-term stability remains a challenge. In this review, we highlight the preclinical performance, structural frameworks, preparation techniques, physicochemical properties, current developments, and prospects of block copolymer micelles as ocular drug delivery systems.

Effectiveness of Adding Dexamethasone to Lidocaine in Upper Limbs Nerve Blocks: A Systematic Review.

PURPOSE: The use of perineural dexamethasone as an adjuvant drug to peripheral nerve block for postoperative pain is controversial. This systematic review aimed to determine the effectiveness of adding dexamethasone to lidocaine in upper limb nerve blocks. DESIGN: Systematic review. METHODS: This review used a comprehensive search strategy to retrieve relevant published randomized trial articles that fulfilled the inclusion and exclusion criteria, without time limits, (until December 2023) that assessed the effects of a combination of dexamethasone to lidocaine in upper limb nerve blocks. The databases used for the electronic literature search included PubMed, Embase, and Clinical Trials.gov, dbGaP, Cochrane library, and Google Scholar. There was no language, gender, or age limitation. This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. FINDINGS: Of 3,926 articles identified by the initial search, 8 studies that met our inclusion criteria. All articles were original research studies. All eight articles were clinical trials. The sample size in the selected studies ranged from 30 to 90 people. Studies demonstrated that combining dexamethasone with lidocaine significantly improved the quality of peripheral nerve blocks, increased the analgesia period, and decreased analgesic consumption. CONCLUSIONS: This review supported that the combination of dexamethasone (dose of 4 to 10 mg) and lidocaine (concentration of 1.5% to 2%) for upper limb block was more effective and beneficial without any side effects. However, further clinical trials in this regard with more data, various regions, and larger sample sizes to support our hypothesis are recommended.

Isoporous Membranes by the Symmetric Triblock Copolymer: A Strategy to Improve the Mechanical Strength without Sharply Changing the Pore Size and Permselectivity.

Isoporous membranes produced from diblock copolymers commonly display a poor mechanical property that shows many negative impacts on their separation application. It is theoretically predicted that dense films produced from symmetric triblock copolymers show much stronger mechanical properties than those of homologous diblock copolymers. However, to the best of our knowledge, symmetric triblock copolymers have rarely been fabricated into isoporous membranes before, and a full understanding of separation as well as mechanical properties of membranes prepared from triblock copolymers and homologous diblock copolymers has not been conducted, either. In this work, a cleavable symmetric triblock copolymer with polystyrene as the side block and poly(4-vinylpyridine) (P4VP) as the middle block was synthesized and designed by the RAFT polymerization using the symmetric chain transfer agent, which located at the center of polymer chains and could be removed to produce homologous diblock copolymers with half-length while having the same composition as that found in triblock copolymers. The self-assembly of these two copolymers in thin films and casting solutions was first investigated, observing that they displayed similar self-organized structures under these two conditions. When fabricated into isoporous membranes, they showed similar pore sizes (5-7% difference) and comparable rejection performance (∼10% difference). However, isoporous membranes produced from triblock copolymers showed significantly improved mechanical strength and higher toughness (2-10 times larger) as evidenced by the compacting resistance, strain-stress determination, and nanoindentation testing, suggesting the unique and novel structure-performance relationship in the isoporous membranes produced from symmetric triblock copolymers. The above finding will guide the way to fabricate mechanically robust isoporous membranes without notably changing the separation performance from rarely used symmetric triblock copolymers, which can be synthesized by the controlled polymerization as facilely as that found for diblock copolymers.

Excellent Electroluminescent Property of Eu3+-Induced Polystyrene-co-poly(acrylic acid) Aggregates (EIPAs) in Polymeric Light-Emitting Diodes.

Eu3+-induced polystyrene-co-poly(acrylic acid) aggregates (EIPAs) were synthesized using a self-assembly approach, and their structures and photophysical characteristics were examined to achieve effective monochromatic red emission in polymer light-emitting diodes (PLEDs). By adjusting the monomer ratio in RAFT polymerization, the size of Eu3+-induced block copolymer nanoaggregates can be regulated, thereby modulating the luminescence intensity. High-performance bilayer polymer light-emitting devices were fabricated using poly(9,9-dioctylfluorene) (PFO) and 2-(tert-butylphenyl)-5-biphenylyl-1,3,4-oxadiazole (PBD) as the host matrix, with EIPAs as the guest dopant. The devices exhibited narrow red emission at 615 nm with a full width at half-maximum (fwhm) of 15 nm across doping concentrations of 1, 3, 5, and 10 wt %. At a doping concentration of 3 wt %, the device achieved a maximum brightness of 1864.48 cd/m2 at 193.82 mA/cm2 and an external quantum efficiency of 3.20% at a current density of 3.5 mA/cm2. These results indicate that incorporating polystyrene-co-poly(acrylic acid) with Eu3+ complexes enhances the excitation and emission intensity, as well as the structural stability of the emitting layer in PLEDs, thereby improving the device performance.

Implementation and optimization of SpMV algorithm based on SW26010P many-core processor and stored in BCSR format.

The irregular distribution of non-zero elements of large-scale sparse matrix leads to low data access efficiency caused by the unique architecture of the Sunway many-core processor, which brings great challenges to the efficient implementation of sparse matrix-vector multiplication (SpMV) computing by SW26010P many-core processor. To address this problem, a study of SpMV optimization strategies is carried out based on the SW26010P many-core processor. Firstly, we design a memorized data storage transformation strategy to transform the matrix in CSR storage format into BCSR (Block Compressed Sparse Row) storage. Secondly, the dynamic task scheduling method is introduced to the algorithm to realize the load balance between slave cores. Thirdly, the LDM memory is refined and designed, and the slave core dual cache strategy is optimized to further improve the performance. Finally, we selected a large number of representative sparse matrices from the Matrix Market for testing. The results show that the scheme has obviously speedup the processing procedure of sparse matrices with various sizes and sizes, and the master-slave speedup ratio can reach up to 38 times. The optimization method used in this paper has implications for other complex applications of the SW26010P many-core processor.

The State-Dependent Channel with a Rate-Limited Cribbing Helper.

The capacity of a memoryless state-dependent channel is derived for a setting in which the encoder is provided with rate-limited assistance from a cribbing helper that observes the state sequence causally and the past channel inputs strictly causally. Said cribbing may increase capacity but not to the level achievable by a message-cognizant helper.

A comparison of fascia iliaca compartment block with intravenous analgesia to improve pain control in patients with femoral fracture.

Background: The most common approach to managing severe pain following femoral fracture is with intravenous systemic analgesics, such as opioid analgesics and non-steroidal anti-inflammatory drugs associated with side effects such as respiratory depression, nausea, and vomiting. These side effects might be intolerable in trauma patients and may result in under treatment of pain. Improving the quality of analgesia may reduce these intolerable side effects. Our study compared the efficacy of fascia iliaca compartment block (FICB) with intravenous analgesics for preoperative pain management of femoral fractures. Patients and Methods: The study was a quality improvement prospective randomised study, where 50 patients aged between 18 and 65 years, and American society of anesthesiologists I and II were recruited into two groups. Group A received FICB with a combination of 0.4 mL/kg of 0.5% plain bupivacaine and adrenaline 1:200,000 made up to 30 mL, while group B received placebo FICB using 30 mL normal saline. Also, group B received a combination of intravenous paracetamol 15 mg/kg not exceeding 900 mg and tramadol 1 mg/kg not exceeding 100 mg, while group A received an equal volume as normal saline intravenously. Results: The study revealed no significant difference in age, gender, associated injuries, X-ray description of fractures, and mechanism of injuries; however, there was a significant difference in the NRS-pain score at 30 min, summed pain intensity difference for 4 h and patient satisfaction in the FICB group compared to the standard group. Conclusion: The study revealed that FICB results in better pain control compared to a combination of intravenous tramadol and paracetamol in patients with femoral fractures.

YOLOv8's advancements in tuberculosis identification from chest images.

Tuberculosis (TB) is a chronic and pathogenic disease that leads to life-threatening situations like death. Many people have been affected by TB owing to inaccuracy, late diagnosis, and deficiency of treatment. The early detection of TB is important to protect people from the severity of the disease and its threatening consequences. Traditionally, different manual methods have been used for TB prediction, such as chest X-rays and CT scans. Nevertheless, these approaches are identified as time-consuming and ineffective for achieving optimal results. To resolve this problem, several researchers have focused on TB prediction. Conversely, it results in a lack of accuracy, overfitting of data, and speed. For improving TB prediction, the proposed research employs the Selection Focal Fusion (SFF) block in the You Look Only Once v8 (YOLOv8, Ultralytics software company, Los Angeles, United States) object detection model with attention mechanism through the Kaggle TBX-11k dataset. The YOLOv8 is used for its ability to detect multiple objects in a single pass. However, it struggles with small objects and finds it impossible to perform fine-grained classifications. To evade this problem, the proposed research incorporates the SFF technique to improve detection performance and decrease small object missed detection rates. Correspondingly, the efficacy of the projected mechanism is calculated utilizing various performance metrics such as recall, precision, F1Score, and mean Average Precision (mAP) to estimate the performance of the proposed framework. Furthermore, the comparison of existing models reveals the efficiency of the proposed research. The present research is envisioned to contribute to the medical world and assist radiologists in identifying tuberculosis using the YOLOv8 model to obtain an optimal outcome.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

Ultrasound-guided serratus anterior plane block enhances postoperative analgesia and recovery in thoracoscopic surgery.

BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.

Isolated Volar Radioulnar Joint Dislocation With Associated Ulnar Styloid Fracture.

Isolated volar dislocation of the distal radioulnar joint is a rare occurrence and is commonly missed. The mechanism of injury typically involves hypersupination. True lateral radiographs are difficult to obtain as patients are usually limited with wrist pronation and supination, resulting in a high miss rate. We describe a 32-year-old male who presented to the emergency department (ED) with pain and swelling of the posteromedial aspect of the right wrist after punching a wall one hour prior to presentation. Examination revealed soft tissue tenderness and mild edema at the right distal ulna with an associated deformity, best visualized at the volar aspect of the right wrist. Active range of motion was limited with right wrist flexion and extension, secondary to pain and edema. Right wrist supination and pronation strength and range of motion were limited due to the patient's tenderness on examination. Peripheral nerve function and vascular examination were normal. Initial radiographs of the right hand, wrist, and forearm did not reveal a fracture or dislocation. A musculoskeletal computed tomography (CT) scan of the right hand and wrist revealed an avulsion fracture of the ulnar styloid with volar displacement of the ulna. Analgesia was achieved with an ultrasound-guided ulnar nerve block, and the right wrist was successfully reduced. This report highlights the difficulty in obtaining a diagnosis of an isolated volar dislocation of the distal radioulnar joint. We recommend obtaining a musculoskeletal CT scan in the setting of an inconclusive radiograph and incongruent physical examination. Analgesia can also be achieved with an ulnar nerve block under ultrasound guidance.

Myocardial Infarction and Complete Heart Block in a Patient With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery (ALCAPA).

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital malformation. We present a case of an elderly patient with ALCAPA presenting with complete heart block and non-ST-elevation myocardial infarction years after diagnosis and surgical correction. An 81-year-old female with a history of ALCAPA presented to the emergency department with chest pain and progressive mental deterioration. She was bradycardic and hypotensive. An electrocardiogram revealed a complete heart block. Troponin was 4.04 ng/mL. She received atropine and underwent transcutaneous pacing. Left heart catheterization revealed complete occlusion of the mid-left circumflex artery, which was intervened with balloon angioplasty and chronic total occlusion of the right coronary artery. She was supported with temporary transvenous pacing, did not require further pacing support, and was discharged home. Previous records unearthed that in 1988 she had presented with syncope and was diagnosed with ALCAPA, filling from right-to-left collaterals with large and ectatic coronaries. At the time, she underwent surgical correction with excision of the left coronary from the pulmonary artery and reimplantation in the left coronary cusp along the posterior aorta. She had remained asymptomatic after her surgery until this presentation. ALCAPA is extremely rare in adults. Insufficient collaterals to the left ventricle cause inadequate blood supply, leading to ischemia in adults, predisposing them to arrhythmias and risk of sudden death. Adults with ALCAPA remain at increased risk of adverse cardiac events later in life, requiring long-term monitoring.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery.

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein ß (S-100ß) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-ß1, TNF-α, and S-100ß were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05). CONCLUSION: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-ß1, TNF-α, and S-100ß levels. This scheme also reduced POCD and had a high safety profile.

Piezo2 voltage-block regulates mechanical pain sensitivity.

PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurones in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved Arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurones isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain of function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurones that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurones innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurones essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurones. Consistently, Piezo2 knock-in mice showed substantial behaviourally hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels.