Effect of Individualized PEEP on Perioperative Pulmonary Complications in Elderly Patients with Prostate Cancer Undergoing General Anesthesia in Trendelenburg Position: A Single-Center Retrospective Study.

OBJECTIVE: This study aimed to explore the effect of individualized positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in elderly patients with prostate cancer undergoing general anesthesia in Trendelenburg position (low-head and high-foot position at about 45° when patients were in supine position). METHODS: The clinical data of 96 elderly patients undergoing Leonardo's robotic-assisted laparoscopic radical prostatectomy in Zhejiang Provincial People's Hospital from October 2021, to April 2023, were selected for retrospective analysis. Sixteen patients who had interrupted follow-up or did not meet the inclusion criteria were excluded, and 80 patients were finally included. The patients were divided into group A (lung-protective strategy using routine PEEP value, n = 40) and group B (lung-protective strategy using individualized PEEP value, n = 40) on the basis of different inversion methods. The PEEP value of group A was set as 5 cmH2O, whereas that of group B was determined under the guidance of static lung compliance. The incidences of PPCs on postoperative day 7 were statistically analyzed, and the serum levels of interleukin (IL) 6 (IL-6) and IL-8 in both groups were measured by enzyme-linked immunoadsordent assay (ELISA). RESULTS: The incidence of pulmonary complications was obviously lower in group B than in group A on postoperative day 7 (p < 0.001). Group B had lower levels of serum IL-6 and IL-8 at the end of surgery (T1) and 12 h after surgery (T2, p < 0.001); Higher oxygenation index values 10 min after successful titration of individualized PEEP (A3), 1 h after individualized PEEP ventilation (A4), 2 h after individualized PEEP ventilation (A5), 10 min after recovery of supine position (A6), and 30 min after tracheal extubation (A7); And lower hospitalization time (all p < 0.001) than group A. CONCLUSIONS: Individualized PEEP for elderly patients with prostate cancer undergoing general anesthesia in Trendelenburg position effectively relieves the release of inflammatory factors, reduces the occurrence of PPCs, and shortens hospitalization time. Thus, it is an effective protection strategy and has certain clinical value.

Effect of Individualized PEEP on Perioperative Pulmonary Complications in Elderly Patients with Prostate Cancer Undergoing General Anesthesia in Trendelenburg Position: A Single-Center Retrospective Study

Objective: This study aimed to explore the effect of individualized positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in elderly patients with prostate cancer undergoing general anesthesia in Trendelenburg position (low-head and high-foot position at about 45° when patients were in supine position). Methods: The clinical data of 96 elderly patients undergoing Leonardo’s robotic-assisted laparoscopic radical prostatectomy in Zhejiang Provincial People’s Hospital from October 2021, to April 2023, were selected for retrospective analysis. Sixteen patients who had interrupted follow-up or did not meet the inclusion criteria were excluded, and 80 patients were finally included. The patients were divided into group A (lung-protective strategy using routine PEEP value, n = 40) and group B (lung-protective strategy using individualized PEEP value, n = 40) on the basis of different inversion methods. The PEEP value of group A was set as 5 cmH2O, whereas that of group B was determined under the guidance of static lung compliance. The incidences of PPCs on postoperative day 7 were statistically analyzed, and the serum levels of interleukin (IL) 6 (IL-6) and IL-8 in both groups were measured by enzyme-linked immunoadsordent assay (ELISA). Results: The incidence of pulmonary complications was obviously lower in group B than in group A on postoperative day 7 (p < 0.001). Group B had lower levels of serum IL-6 and IL-8 at the end of surgery (T1) and 12 h after surgery (T2, p < 0.001); Higher oxygenation index values 10 min after successful titration of individualized PEEP (A3), 1 h after individualized PEEP ventilation (A4), 2 h after individualized PEEP ventilation (A5), 10 min after recovery of supine position (A6), and 30 min after tracheal extubation (A7); And lower hospitalization time (all p < 0.001) than group A (AU)

NPM3 as an unfavorable prognostic biomarker involved in oncogenic pathways of lung adenocarcinoma via MYC translational activation.

BACKGROUND: The nucleoplasmin/nucleophosmin (NPM) family was previously regarded as a critical regulator during disease development, and its mediation in carcinogenesis has achieved intensive attention recently. However, the clinical importance and functional mechanism of NPM3 in lung adenocarcinoma (LUAD) have not been reported yet. OBJECTIVE: This study aimed to investigate the role and clinical significance of NPM3 in the development and progression of LUAD, including the underlying mechanisms. METHOD: The expression of NPM3 in pan-cancer was analyzed via GEPIA. The effect of NPM3 on prognosis was analyzed by the Kaplan-Meier plotter and the PrognoScan database. In vitro, cell transfection, RT-qPCR, CCK-8 assay, and wound healing assay were employed to examine the role of NPM3 in A549 and H1299 cells. Gene set enrichment analysis (GSEA) was performed using the R software package to analyze the tumor hallmark pathway and KEGG pathway of NPM3. The transcription factors of NPM3 were predicted based on the ChIP-Atlas database. Dual-luciferase reporter assay was applied to verify the transcriptional regulatory factor of the NPM3 promoter region. RESULTS: The NPM3 expression was found to be markedly higher in the LUAD tumor group than the normal group and to be positively correlated with poor prognosis, tumor stages, and radiation therapy. In vitro, the knockdown of NPM3 greatly inhibited the proliferation and migration of A549 and H1299 cells. Mechanistically, GSEA predicted that NPM3 activated the oncogenic pathways. Further, the NPM3 expression was found to be positively correlated with cell cycle, DNA replication, G2M checkpoint, HYPOXIA, MTORC1 signaling, glycolysis, and MYC targets. Besides, MYC targeted the promoter region of NPM3 and contributed to the enhanced expression of NPM3 in LUAD. CONCLUSION: The overexpression of NPM3 is an unfavorable prognostic biomarker participating in oncogenic pathways of LUAD via MYC translational activation and it contributes to tumor progression. Thus, NPM3 could be a novel target for LUAD therapy.

Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. METHODS: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. RESULTS: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. CONCLUSIONS: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.

Dexmedetomidine pretreatment alleviates ropivacaine-induced neurotoxicity via the miR-10b-5p/BDNF axis.

BACKGROUND: Ropivacaine is commonly applied for local anesthesia and may cause neurotoxicity. Dexmedetomidine (DEX) exhibits neuroprotective effects on multiple neurological disorders. This study investigated the mechanism of DEX pretreatment in ropivacaine-induced neurotoxicity. METHODS: Mouse hippocampal neuronal cells (HT22) and human neuroblastoma cells (SH-SY5Y) were treated with 0.5 mM, 1 mM, 2.5 mM, and 5 mM ropivacaine. Then the cells were pretreated with different concentrations of DEX (0.01 µM, 0.1 µM, 1 µM, 10 µM, and 100 µM) before ropivacaine treatment. Proliferative activity of cells, lactate dehydrogenase (LDH) release, and apoptosis rate were measured using CCK-8 assay, LDH detection kit, and flow cytometry, respectively. miR-10b-5p and BDNF expressions were determined using RT-qPCR or Western blot. The binding of miR-10b-5p and BDNF was validated using dual-luciferase assay. Functional rescue experiments were conducted to verify the role of miR-10b-5p and BDNF in the protective mechanism of DEX on ropivacaine-induced neurotoxicity. RESULTS: Treatment of HT22 or SH-SY5Y cells with ropivacaine led to the increased miR-10b-5p expression (about 1.7 times), decreased BDNF expression (about 2.2 times), reduced cell viability (about 2.5 times), elevated intracellular LDH level (about 2.0-2.5 times), and enhanced apoptosis rate (about 3.0-4.0 times). DEX pretreatment relieved ropivacaine-induced neurotoxicity, as evidenced by enhanced cell viability (about 1.7-2.0 times), reduced LDH release (about 1.7-1.8 times), and suppressed apoptosis rate (about 1.8-1.9 times). DEX pretreatment repressed miR-10b-5p expression (about 2.5 times). miR-10b-5p targeted BDNF. miR-10b-5p overexpression or BDNF silencing reversed the protective effect of DEX pretreatment on ropivacaine-induced neurotoxicity, manifested as reduced cell viability (about 1.3-1.6 times), increased intracellular LDH level (about 1.4-1.7 times), and elevated apoptosis rate (about 1.4-1.6 times). CONCLUSIONS: DEX pretreatment elevated BDNF expression by reducing miR-10b-5p expression, thereby alleviating ropivacaine-induced neurotoxicity.

The efficacy and safety of denosumab in postmenopausal women with osteoporosis previously treated with bisphosphonates: A review.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of denosumab therapy in osteoporotic postmenopausal women who were previously treated with bisphosphonates. METHODS: Meta-analyses of four available randomised controlled trials that compared osteoporotic patients who switched to denosumab from bisphosphonates (n â€‹= â€‹1416) and those who continued bisphosphonates therapy (n â€‹= â€‹1411) were included. RESULTS: The increase in bone mineral density (BMD) of both the spine and hip was significantly higher in patients who shifted to denosumab than in those who continued bisphosphonates. Despite the incidence of adverse events (AEs) and fractures being comparable, treatment withdrawal owing to AEs was significantly less frequent in the denosumab group. CONCLUSION: The outcomes and treatment compliance were improved in postmenopausal osteoporotic women who shifted to denosumab from bisphosphonates. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The replacement of bisphosphonates with denosumab may lead to better therapeutic efficacy and fewer adherence barriers â€‹than those with continued usage of bisphosphonates, which in the future may guide the choice of drug therapy in clinics.

High-resolution bimodal imaging and potent antibiotic/photodynamic synergistic therapy for osteomyelitis with a bacterial inflammation-specific versatile agent.

Unsatisfactory diagnosis and therapy of osteomyelitis are still common but challenging issues for clinicians. To overcome these problems, a bacterial inflammation-specific multifunctional agent, denoted bovine serum albumin-manganese dioxide-ubiquicidin29-41-indocyanine green (ICG) -gentamicin (BMUIG), was synthesized for combined high-resolution bimodal imaging and antibiotic/photodynamic therapy for osteomyelitis. BMUIG binding affinity and antibacterial ability were assessed by using Staphylococcus aureus (S. aureus). Photoacoustic/magnetic resonance imaging was performed on a mouse model of acute osteomyelitis after intravenous injection of BMUIG. Then, myelitis-bearing mice were treated with antibiotic/photodynamic combination therapy. BMUIG specifically targeted S. aureus in comparison with non-targeted agents. In the osteomyelitis model, the infection area was identified accurately and quickly through ICG-based photoacoustic imaging and Mn2+-based T1 magnetic resonance imaging after injection of BMUIG. Furthermore, the manganese dioxide in BMUIG reacted with the locally produced hydrogen peroxide under acidic inflammatory conditions, continuously generating oxygen for enhanced photodynamic therapy. In combination with low-dose gentamicin, a synergistic antibacterial effect was observed and bone infection was resolved. In summary, a non-invasive accurate diagnosis and effective synergistic therapy for osteomyelitis was successfully developed using a bacterial inflammation-specific versatile agent, which would provide a sound theranostic strategy for common infectious diseases. STATEMENT OF SIGNIFICANCE: Osteomyelitis is one of the most serious consequences in orthopedics. However, its inaccurate diagnosis and low-effective antibiotic treatment are still common but challenging issues for clinicians. To overcome these problems, we uniquely designed a bacterial inflammation-specific multifunctional nanoagent, bovine serum albumin-manganese dioxide-ubiquicidin29-41-indocyanine green-gentamicin (BMUIG), for high-resolution bimodal imaging and antibiotic/photodynamic combined therapy of osteomyelitis. Herein, high-resolution imaging technologies refer to classic magnetic resonance imaging and emerging photoacoustic imaging. Photodynamic therapy is subtly introduced because of its safe and effective killing mechanism, which can synergize the bactericidal effect of antibiotics. As a result, we successfully realize non-invasive accurate diagnosis and effective synergistic therapy for osteomyelitis by virtue of the bacterial inflammation-specific versatile agent, which will serve as a promising candidate for sound theranostics in common infectious diseases.

Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory, anti-hyperuricemic, and NLRP3 inhibition.

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia. Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia. Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1ß & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside. Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1ß and NLRP3 expression. Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.

Knockdown of FOXM1 attenuates inflammatory response in human osteoarthritis chondrocytes.

Osteoarthritis (OA) is the most common inflammatory joint disease that is mainly characterized by articular cartilage destruction. Forkhead box M1 (FOXM1) is a transcription factor that acts as a critical mediator of inflammatory response. However, the role of FOXM1 in OA has not been investigated. Interleukin (IL)-1ß is a major proinflammatory cytokine, which is associated with cartilage destruction in the pathophysiology of OA. In the present study, we used IL-1ß to stimulate chondrocytes for the establishment of OA in vitro model. We found that FOXM1 was up-regulated in IL-1ß-induced chondrocytes. Knockdown of FOXM1 attenuated IL-1ß-caused decrease in cell viability. Knockdown of FOXM1 suppressed the IL-1ß-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, and IL-6. Besides, several inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2) were also repressed by knockdown of FOXM1. FOXM1 silencing also inhibited the production of matrix metalloproteinases (MMPs) including MMP-3 and MMP-13. Furthermore, we found that knockdown of FOXM1 blocked the IL-1ß-induced NF-κB activation in chondrocytes. These findings indicated that FOXM1 might play an important role in the pathogenesis of OA, suggesting that FOXM1 might be a potential therapeutic target for the treatment of OA.

Postoperative serum thioredoxin concentrations correlate with delirium and cognitive dysfunction after hip fracture surgery in elderly patients.

BACKGROUND: Oxidative stress correlates with occurrence and development of postoperative delirium (POD) and cognitive dysfunction (POCD). Thioredoxin (TRX) is a potent anti-oxidant and its circulating concentrations reflect extent of brain injury. We determined the relation of serum TRX concentrations to POD and POCD in elderly patients undergoing hip fracture surgery. METHODS: In this prospective, observatory study, TRX concentrations in preoperative and postoperative serum from 192 patients and serum from 192 controls were measured using an enzyme-linked immunosorbent assay. The relationship between TRX concentrations and risk of POD and POCD was assessed using a multivariate analysis. RESULTS: As compared to the controls, postoperative, but not preoperative serum TRX concentrations were significantly increased in the patients. Furthermore, postoperative TRX concentrations and age were identified as the independent predictors for POD and POCD. Also, area under receiver operating characteristic curve (AUC) of postoperative TRX concentrations was obviously higher than that of age in the prediction of POD and POCD. Additionally, in a combined logistic-regression model, TRX concentrations significantly improved the AUCs of age to predict POD and POCD. CONCLUSIONS: TRX in postoperative serum may be a potential biomarker to predict POD and POCD in elder patients undergoing hip fracture surgery.

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling.

It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.

Automatic clocking optimization for compensating two-dimensional tolerances.

Clocking of lens elements is frequently used as an effective method of compensating for two-dimensional tolerances such as material inhomogeneity and surface figure errors. Typically, the lens designer has to determine the optimum angles of rotation by manually modeling lens element clocking in the commercial optical design software because the nature of errors resolved by lens clocking does not lead to good convergences for clocking optimization. In this paper, a method of automatic clocking optimization is developed. The method is implemented using a combination of particle swarm optimization algorithm and commercial optical design software. The optimum angles of rotation and predicted imaging performance are automatically calculated using this method. Methods of implementation and optimization examples are also given.

Wavefront aberration compensation of projection lens using clocking lens elements.

For extremely high-performance lithographic lenses, the edge level accuracy of the manufacturing process and multicompensation strategies must be applied. Element clocking can be effectively used to compensate for the low-order figure errors of the elements. Considering that commercial optical software is usually incapable of obtaining good convergence for clocking optimization, this paper proposes a mathematical model of a lithographic lens containing the errors of a surface figure, after which a clocking optimization algorithm is programmed. A clocking optimization instance proving that the clocking optimization algorithm is capable of finding the optimized angle of elements and that clocking is an effective compensation strategy. The calculated accuracy of the proposed mathematic model was found to be acceptable for clocking optimization.

Intermodal interferometer based on a fluid-filled two-mode photonic crystal fiber for sensing applications.

A fluid-filled two-mode photonic crystal fiber (PCF)-based intermodal interferometer and its sensing characteristics are demonstrated and investigated. The interferometer works from the interference between LP(01) and LP(11) core modes of the fluid-filled PCF. Solutions to enhance the temperature sensitivity of the interferometer are also discussed. Via choosing a higher fluid-filled length ratio of PCF, a sensitivity of more than -340 pm/°C at 1480 nm is achieved, which is the highest value for a PCF intermodal interferometer-based sensor, to our best knowledge. Furthermore, there exist significant differences in temperature and strain sensitivity for two different interference dips, thus the interferometer can be used as a dual-parameter sensor with a compact structure through matrix demodulation.

[Investigation on hantaviruses infection in rodents from free markets in Beijing areas].

OBJECTIVE: In order to find out the factors related to hemorrhagic fever with renal syndrome (HFRS) infection, and to evaluate the probability of ecdemic hantaviruses (HV) infection in rodents in Beijing areas. METHODS: Rodents were collected in a large-scale railway station and a produce market with 'trap nights' method from April to May, 2004. The IgG reacting sera to HV antigen were detected using ELISA. The partial M and S segment of HV from captured rodent lung samples were amplified with RT-PCR. The PCR products were purified and sequenced. BLAST program was then used to perform on nucleotide pairwise alignment with all available sequence in GenBank. The alignment of the multiply nucleotide and the deduced amino acid sequences, together with phylogenetic analysis were completed with DNASTAR software. RESULTS: The average population density was 3.49% (24/690). The overall seroprevalence of HV infection was 8.3% (2/24). RT-PCR positive rates were 8.3% (2/24). The nucleotide sequences of 356 bp region (1958 - 2313) of M segment obtained from 2 samples were all identified to Seoul virus (SEOV), with 7.6% heterogeneity. The dc501 strain from railway station was closely related to SD227 and Hebei4 from Shandong and Hebei provinces respectively. BjFT01 strain from the farm product market had more special nucleotide transitional mutations than other known SEOV from Beijing in GenBank. This strain, together with known HN71 from Hainan province, K24-E7 from Zhejiang province, L99 from Jiangxi province and R22 from Henan province, represented a monophylogentic linkage. CONCLUSION: The higher HV prevalence of rodents in transportation center was the potential and important risk for HFRS epidemic in Beijing. The increasing prevalence of M. musculus should call for attention. It was possible that SEOV in Beijing was imported by infected rodents through vehicles from other provinces.