SARS-CoV-2 reinfection broadens the antibody responses and promotes the phenotypic differentiation of virus-specific memory T cells in adolescents.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.

Humoral and cellular immune responses following Omicron BA.2.2 breakthrough infection and Omicron BA.5 reinfection.

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.

Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. METHODS: We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves. RESULTS: There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI-lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI-lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. CONCLUSION: 18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis.

BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB. METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level. FINDINGS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species. INTERPRETATION: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions. FUNDING: National Key Research and Development Program of China.

THE PROTECTIVE EFFECT OF DEXMEDETOMIDINE ON THE LIVER INJURY IN SEPSIS THROUGH INHIBITION OF NECROPTOSIS.

ABSTRACT: Background: Sepsis-induced liver injury leads to extensive necroptosis in hepatocytes, which is the main factor of liver dysfunction. This study aims to investigate the protective effect of dexmedetomidine (DEX) on septic liver and to explore whether its molecular mechanism is related to the modulation of necroptosis. Methods: The model of septic liver injury was induced by cecal ligation and puncture (CLP) in rats. DEX and necrostatin-1(Nec-1), a specific antagonist of necroptosis, were administered 1 h before CLP. The levels of arterial blood gas, serum aspartate aminotransferase, and alanine aminotransferase were measured at 6, 12 and 24 h after CLP. The survival rate was observed 24 h after CLP. Liver pathological changes and apoptosis, the contents of IL-6 and TNF-α in liver tissue homogenates, the ROS content in liver tissue, and the expression levels of RIP1, RIP3, MLKL, and HMGB1 were detected. Results: At 6, 12, and 24 h after CLP, the levels of aspartate aminotransferase, and alanine aminotransferase levels increased, and liver enzyme levels gradually increased with the progression of sepsis. In arterial blood gas analysis, P a O 2 gradually decreased and lactic acid concentration gradually increased during these three periods. The morphological impairment of liver tissues, increased apoptosis, elevated inflammatory factors (IL-6 and TNF-α), increased ROS level, and necroptosis components (RIP1, RIP3, MLKL, and HMGB1) were all observed in sepsis rats. However, these injuries can be ameliorated by pretreatment with DEX. Meanwhile, Nec-1 pretreatment also reduced the expression of RIP1, RIP3, MLKL, HMGB1, and ROS level. Conclusion: Our study suggests that DEX alleviates septic liver injury, and the mechanism is associated with the inhibition of necroptosis.

A novel lifting point location optimization method of transmission line tower based on improved grey wolf optimizer.

In the erection process of transmission line tower, the appropriate lifting point position is an important factor in ensuring the stability and balance of the lifting process and preventing deformation and damage to the towers. In this paper, a improved grey wolf optimization algorithm is proposed to solve the issues of low optimization efficiency and easily getting trapped in local minima when optimizing the lifting point position of transmission line towers. The improved algorithm includes the use of a good point-set strategy to enhance the initialization method of grey wolf individuals, ensuring a more uniform distribution of the population and reducing ineffective searches in the early stages of optimization. Furthermore, two random operators are utilized to combine and mutate the optimal grey wolf position, thereby enhancing the algorithm's ability to escape local optima. Finally, the trend information of the optimization process is considered, and the median value of the population is used to improve the stability of the optimization algorithm. Experimental results demonstrate that the proposed algorithm has better optimization performance and faster convergence speed compared to genetic algorithm, particle swarm optimization algorithm, and artificial fish swarm algorithm. It effectively addresses the optimization problem of lifting point position for transmission line towers.

Zoonotic pathogens identified in rodents and shrews from four provinces, China, 2015-2022.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Association between furosemide administration and clinical outcomes in patients with sepsis-associated acute kidney injury receiving renal replacement therapy: a retrospective observational cohort study based on MIMIC-IV database.

OBJECTIVE: To investigate the association between furosemide administration and clinical outcomes in patients with sepsis-associated acute kidney injury (SAKI) receiving renal replacement therapy (RRT). DESIGN: A retrospective observational cohort study. SETTING: The data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which contains clinical data from more than 380 000 patients admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center from 2008 to 2019. PARTICIPANTS: All adult patients with SAKI receiving RRT were enrolled. Data for each patient within the first 24 hours of ICU admission were extracted from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was in-hospital mortality, and the secondary outcome was the length of hospital stay, length of ICU stay, RRT-free time and ventilator-free time. Logistic regression was used to investigate the association between furosemide administration and in-hospital mortality. Subgroup analysis was employed to explore the potential sources of heterogeneity. RESULTS: A total of 1663 patients with SAKI receiving RRT were enrolled in the study, of whom 991 patients (59.6%) were retrospectively allocated to the Furosemide group and 672 (40.4%) patients to the non-furosemide group. Univariate and multivariate logistic regression showed that furosemide administration was associated with reduced in-hospital mortality, respectively ((OR 0.77; 95% CI 0.63 to 0.93; p=0.008 < 0.05), (OR 0.59; 95% CI 0.46 to 0.75; p<0.001)). The association remained robust to different ways of adjusting for baseline confounding (all p<0.05). Subgroup analysis suggested that AKI-stage may be a source of heterogeneity. Patients in the furosemide group also had longer RRT-free time (p<0.001) and longer ventilator-free time (p<0.001) than those in the non-furosemide group. CONCLUSIONS: Furosemide is associated with decreased in-hospital mortality, longer RRT-free time and ventilator-free time in patients with SAKI receiving RRT.

Safety and effectiveness of the combination of remimazolam tosilate and propofol in gastroscopy: a multicenter, randomized controlled, single-blind clinical trial.

Remimazolam tosilate (RT) is a new short-acting γ-aminobutyric acid A (GABAA) receptors agonist. However, its optimal use mode and dosage still remain unclear. This study aimed to examine the safety and effectiveness of the combination of RT and propofol in gastroscopy. This was a prospective, single-blind, randomized, multicenter, parallel-group study. All eligible 256 patients were randomized into the following 3 groups. Patients were anesthetized with propofol (Group P), RT (Group R) or the combination of RT and propofol (Group RP). The primary efficacy endpoints were: body movement score; satisfaction of gastroscopy doctors; success rate of sedation and effects on sleep status. Sedation induction time, time to be fully alert and adverse events were also recorded. The probability of complete immobility was lower in group R (33.73%) than in group P (86.67%) and RP (83.13%). The rate of doctors' satisfaction was much lower in group R (28.92%) than in group P (77.78%) and RP (72.29%). The success rate of sedation and sleep outcome score has no difference in the three groups. The time to adequate sedation was longer in group RP (77.27 ± 18.63 s) than in group P (64.47 ± 24.36 s), but much shorter than that in group R (102.84 ± 46.43s). The time to be fully alert was shorter in group R (6.30 ± 1.52 min) and RP (6.54 ± 1.13 min) than in group P (7.87 ± 1.08 min). The proportion of sedative hypotension was significantly higher in group P (41.11%) than in group R (1.20%) and group RP (3.61%) (p < 0.001). The incidence of respiratory depression was much higher in group P (17.78%) than in group R (no patient) and group RP (1.2%). The incidence of adverse events was lower in groups R (4.82%) and RP (9.64%) than in group P (31.11%). The combination of RT and propofol takes effect quickly, makes patients alert quickly, provides a sufficient depth of sedation, reduces body movement, does not inhibit circulation and respiratory function, does not affect sleep, and is the preferred mode for gastroscopy doctors and anesthesiologists.

Prevalence and Etiological Characteristics of Norovirus Infection in China: A Systematic Review and Meta-Analysis.

Norovirus is a common cause of sporadic cases and outbreaks of gastroenteritis worldwide, although its prevalence and the dominant genotypes responsible for gastroenteritis outbreaks remain obscure. A systematic review was conducted on norovirus infection in China between January 2009 and March 2021. A meta-analysis and beta-binomial regression model were used to explore the epidemiological and clinical characteristics of norovirus infection and the potential factors contributing to the attack rate of the norovirus outbreaks, respectively. A total of 1132 articles with 155,865 confirmed cases were included, with a pooled positive test rate of 11.54% among 991,786 patients with acute diarrhea and a pooled attack rate of 6.73% in 500 norovirus outbreaks. GII.4 was the predominant genotype in both the etiological surveillance and outbreaks, followed by GII.3 in the etiological surveillance, and GII.17 in the outbreaks, with the proportion of recombinant genotypes increasing in recent years. A higher attack rate in the norovirus outbreaks was associated with age group (older adults), settings (nurseries, primary schools, etc.) and region (North China). The nation-wide pooled positive rate in the etiological surveillance of norovirus is lower than elsewhere in the global population, while the dominant genotypes are similar in both the etiological surveillance and the outbreak investigations. This study contributes to the understanding of norovirus infection with different genotypes in China. The prevention and control of norovirus outbreaks during the cold season should be intensified, with special attention paid to and enhanced surveillance performed in nurseries, schools and nursing homes from November to March.

[18F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors.

Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers. Methods: In this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo. Results: Radiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor. Conclusion: [18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.

Viscoelastic Numerical Simulation Study on the Co-Extrusion Process of Tri-Composite Tire Tread.

The co-extrusion process is widely used to produce composite tire treads with better performance. This study investigated the rubber co-extrusion flow process and quality influencing factors of tri-composite tire tread through numerical simulation and experimental methods. Here, RPA 2000 rubber processing analyzer was used to carry out rheological tests on the three rubber materials, the PTT viscoelastic constitutive model was fitted, and the fitting curves were in good agreement with the test data. Then, a three-dimensional viscoelastic numerical simulation model of the tri-composite tread co-extrusion process was established using Ansys Polyflow software. The parameter evolution technique is adopted in the model establishment to improve the calculation convergence. In addition, a global remeshing function is used to avoid excessive mesh deformation. A co-extrusion experiment is conducted to verify the model's accuracy using a tri-screw extruder. The extruded tread size error rate between the experiment and simulation is less than 6%. The variation of the velocity field, pressure field and shear rate field during extrusion is analyzed, and the formation mechanism of die swell is explained simultaneously. Finally, the influence of process parameters (inflow rate and traction speed) and die structure (convergence angle and thickness) on the extruded tire tread shape and quality was investigated, which can provide theoretical guidance for improving tread quality and production efficiency. Furthermore, the numerical simulation method can assist the design of the die plate in enhancing the efficiency of the die plate design.

Spinal microRNA-134-5p targets glutamate receptor ionotropic kainate 3 to modulate opioid induced hyperalgesia in mice.

Background: Fentanyl and its analogs are extensively used for pain relief. However, their paradoxically pronociceptive effects often lead to increased opioids consumption and risk of chronic pain. Compared to other synthetic opioids, remifentanil has been strongly linked to acute opioid hyperalgesia after exposure [remifentanil-induced hyperalgesia (RIH)]. The epigenetic regulation of microRNAs (miRNAs) on targeted mRNAs has emerged as an important pathogenesis in pain. The current research aimed at exploring the significance and contributions of miR-134-5p to the development of RIH. Methods: Both the antinociceptive and pronociceptive effects of two commonly used opioids were assessed, and miRNA expression profiles in the spinal dorsal horn (SDH) of mice acutely exposed to remifentanil and remifentanil equianalgesic dose (RED) sufentanil were screened. Next, the candidate miRNA level, cellular distribution, and function were examined by qPCR, fluorescent in situ hybridization (FISH) and Argonaute-2 immunoprecipitation. Furthermore, bioinformatics analysis, luciferase assays, miRNA overexpression, behavioral tests, golgi staining, electron microscopy, whole-cell patch-clamp recording, and immunoblotting were employed to investigate the potential targets and mechanisms underlying RIH. Results: Remifentanil induced significant pronociceptive effects and a distinct miRNA-profile from sufentanil when compared to saline controls. Among top 30 differentially expressed miRNAs spectrum, spinal miR-134-5p was dramatically downregulated in RIH mice but remained comparative in mice subjected to sufentanil. Moreover, Glutamate Receptor Ionotropic Kainate 3 (Grik3) was a target of miR-134-5p. The overexpression of miR-134-5p attenuated the hyperalgesic phenotype, excessive dendritic spine remodeling, excitatory synaptic structural plasticity, and Kainate receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in SDH resulting from remifentanil exposure. Besides, intrathecal injection of selective KA-R antagonist was able to reverse the GRIK3 membrane trafficking and relieved RIH. Conclusion: The miR-134-5p contributes to remifentanil-induced pronociceptive features via directly targeting Grik3 to modulate dendritic spine morphology and synaptic plasticity in spinal neurons.

Effects of qCON and qNOX-guided general anaesthesia management on patient opioid use and prognosis: a study protocol.

INTRODUCTION: The adverse effects of general anaesthetic drugs (especially opioids) cannot be ignored. However, current nociceptive-monitoring techniques still lack consistency in guiding the use of opioids. This trial will study the demand for opioid use and patient prognosis in qCON and qNOX-guided general anaesthesia management. METHODS AND ANALYSIS: This prospective, randomised, controlled trial will randomly recruit 124 patients undergoing general anaesthesia for non-cardiac surgery in equal numbers to either the qCON or BIS group. The qCON group will adjust intraoperative propofol and remifentanil dosage according to qCON and qNOX values, while the BIS group will adjust according to BIS values and haemodynamic fluctuations. The differences between the two groups will be observed in remifentanil dosing and prognosis. The primary outcome will be intraoperative remifentanil use. Secondary outcomes will include propofol consumption; the predictive ability of BIS, qCON and qNOX on conscious responses, noxious stimulus and body movements; and changes in cognitive function at 90 days postoperatively. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2022-YX-075-01). Participants gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059877.