RESUMO
BACKGROUND: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. RESULTS: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. CONCLUSIONS: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.
Assuntos
Infecções por Circoviridae , Circovirus , Doenças do Cão , Filogenia , Animais , Circovirus/genética , Circovirus/classificação , Cães , Doenças do Cão/virologia , Doenças do Cão/epidemiologia , China/epidemiologia , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/virologia , Evolução Molecular , Genoma Viral , Variação Genética , Prevalência , GenótipoRESUMO
Numerous genome-wide association studies have identified risk genes for chronic pain, yet the mechanisms by which genetic variants modify susceptibility have remained elusive. We sought to identify key genes modulating chronic pain risk by regulating brain protein expression. We integrated brain proteomic data with the largest genome-wide dataset for multisite chronic pain (N = 387,649) in a proteome-wide association study (PWAS) using discovery and confirmatory proteomic datasets (N = 376 and 152) from the dorsolateral prefrontal cortex. Leveraging summary data-based Mendelian randomization and Bayesian colocalization analysis, we pinpointed potential causal genes, while a transcriptome-wide association study integrating 452 human brain transcriptomes investigated whether cis-effects on protein abundance extended to the transcriptome. Single-cell RNA-sequencing data and single-nucleus transcriptomic data revealed cell-type-specific expression patterns for identified causal genes in the dorsolateral prefrontal cortex and dorsal root ganglia (DRG), complemented by RNA microarray analysis of expression profiles in other pain-related brain regions. Of the 22 genes cis-regulating protein abundance identified by the discovery PWAS, 18 (82%) were deemed causal by summary data-based Mendelian randomization or Bayesian colocalization analysis analyses, with 7 of these 18 genes (39%) replicating in the confirmatory PWAS, including guanosine diphosphate-mannose pyrophosphorylase B, which also associated at the transcriptome level. Several causal genes exhibited selective expression in excitatory and inhibitory neurons, oligodendrocytes, and astrocytes, while most identified genes were expressed across additional pain-related brain regions. This integrative proteogenomic approach identified 18 high-confidence causal genes for chronic pain, regulated by cis-effects on brain protein levels, suggesting promising avenues for treatment research and indicating a contributory role for the DRG. PERSPECTIVE: The current post genome-wide association study analyses identified 18 high-confidence causal genes regulating chronic pain risk via cis-modulation of brain protein abundance, suggesting promising avenues for future chronic pain therapies. Additionally, the significant expression of these genes in the DRG indicated a potential contributory role, warranting further investigation.
RESUMO
An effective approach for the large-scale fabrication of conducting polyaniline (PANI) using in situ anodic electrochemical polymerization on nickel foam which had been coated in aryl diazonium salt (ADS)-modified graphene (ADS-G). In the present work, ADS-G was used as a high surface-area support material for the electrochemical polymerization of PANI. The electrochemical performances of the ADS-G/PANI composites exhibited better suitability as supercapacitor electrode materials than those of the PANI. The ADS-G/PANI composites achieved a specific capacitance of 528 F g-1, which was higher than that of PANI (266 F g-1) due to excellent electrode-electrolyte interaction and the synergistic effect of electrical conductivity between ADS-G and PANI in the composites. These findings suggest that the ADS-G/PANI composites are a suitable composite for potential supercapacitor applications.
RESUMO
The present study aimed to investigate the association between intraoperative body temperature and prolonged length of stay (PLOS) after free flap reconstruction. A total of 753 patients who underwent head and neck surgery with free flap reconstruction were collected and randomly assigned into primary and validation cohorts. In the primary cohort, univariable and multivariable analyses were conducted to evaluate associations between intraoperative time-weighted (TW) temperature (TW average [TWA] temperature, TW hypothermia and TW hyperthermia) and PLOS. Nomograms were developed with and without intraoperative TW temperature, and validated in the validation cohort. Severe intraoperative TW hypothermia (OR = 1.004; 95% CI: 1.000, 1.007; p = 0.032) was identified as an independent risk factor for PLOS. Intraoperative TWA temperature and TW hypothermia showed linear related predictive effect for PLOS. The nomogram incorporating intraoperative TW temperature showed higher C-index (0.652, 95% CI: 0.591, 0.713) and improved net reclassification improvement for non-event (0.277, 95% CI: 0.118, 0.435; p < 0.001). Lower TWA temperature with mild TW hypothermia had a preventive effect on PLOS with a linear association, which may provide a modified range for intraoperative temperature management. The proposed nomogram incorporating intraoperative TW temperature could be used to develop personalized preventive strategies for PLOS after free flap reconstruction. IRB NUMBER: SYSEC-KY-KS-2022-037. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Hipotermia , Humanos , Hipotermia/complicações , Temperatura , Tempo de Internação , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologiaRESUMO
ABSTRACT: Background: Furosemide is a commonly used loop diuretic in critical care. However, its effect on the progression of oliguric acute kidney injury across different central venous pressure (CVP) remains unknown. This study therefore aims to investigate the association between furosemide 6-12h (defined as the use of furosemide within 6 h after the diagnosis of AKI according to the urine output [UO] criteria set by the Kidney Disease: Improving Global Outcomes [KDIGO] guidelines) and the progression of AKI across different CVP 6-12h (defined as CVP within 6 h after the diagnosis of AKI by the KDIGO UO criteria) levels. Methods: Patients involved in this study were identified from the Medical Information Mart for Intensive Care IV database with the following criteria: (i) adults with UO <0.5 mL/kg per hour for the first 6 h upon admission to the intensive care unit (ICU) (meeting stage 1 AKI by UO) and (ii) CVP 6-12h ranging from 0 to 30 mm Hg. From there on, the target primary outcome would be progression to stage 3 AKI by UO among these chosen patients. The secondary outcome was 28-d mortality since ICU admission. The risks of severe-stage AKI progression and 28-d mortality were respectively examined against furosemide 6-12h (vs. without furosemide 6-12h ) within the full cohort and across different subgroups of CVP 6-12h , using multivariate adjusted logistic regression and inverse probability treatment weighting (IPTW). Sensitivity analyses were performed to assess the robustness of our findings. Results: One thousand one hundred eighty patients were ultimately selected for this study, of whom 643 (54.5%) progressed to stage 3 AKI from stage 1 based on the UO criteria by KDIGO. Multivariate analysis showed that furosemide 6-12h is significantly associated with this severe-stage progression within the full cohort (odds ratio [OR] was 0.62 at 95% confidence interval [CI] of 0.43-0.90, P = 0.011). After dividing the patients into CVP 6-12h subgroups according to their CVP during the early phases, lower risk of AKI progression was observed only in furosemide 6-12h application at CVP 6-12h of ≥12 mm Hg (adjusted OR was 0.40 at 95% CI of 0.25-0.65, P < 0.001), as confirmed by the IPTW analysis (OR was 0.47 at 95% CI of 0.29-0.76, P = 0.002). The robustness of these findings was confirmed by sensitivity analyses. In addition, for patients with CVP 6-12h ≥12 mm Hg, furosemide 6-12h is also significantly associated with lower risk of 28-d mortality (adjusted OR was 0.47 at 95% CI of 0.25-0.92, P = 0.026) in the multivariate logistic regression analysis, and there was a similar trend in the IPTW analysis (adjusted OR was 0.55 at 95% CI of 0.28-1.10, P = 0.092). Conclusions: Among the identified early-stage AKI patients in critical care, the use of furosemide was associated only with lower risk of oliguric AKI progression and 28-d mortality within the high CVP group. These findings suggest the potential of CVP as a guidance or reference point in the usage of furosemide among early-stage oliguric AKI patients in the ICU.
Assuntos
Injúria Renal Aguda , Furosemida , Adulto , Humanos , Furosemida/uso terapêutico , Pressão Venosa Central , Estudos Retrospectivos , Unidades de Terapia Intensiva , Injúria Renal Aguda/tratamento farmacológicoRESUMO
OBJECTIVES: To find out the occurrence rate and risk factors of unplanned reoperation (any unscheduled surgery within 30 d after the initial surgery) in patients who have received oral squamous cell carcinoma (OSCC) surgery and vascularized free flap reconstruction. PATIENTS AND METHODS: We organized a retrospective study of 1058 patients who underwent OSCC resection and reconstruction with vascularized free flaps from 2011 to 2019. Clinical characteristics, reasons for unplanned reoperation, flap types, and previous treatment were compared between the unplanned reoperation group and the control group. Univariate and multivariate analyses were performed to identify perioperative risk factors for unplanned reoperation. The related perioperative factors that may influence perioperative infusion were included in propensity score matching to investigate the independent contribution of intraoperative colloid infusion on unplanned reoperation. RESULTS: The overall rate of unplanned reoperation in OSCC patients was 11% (n=115). Flap necrosis and bleeding were the most common causes. Higher American Society of Anesthesiologists (ASA) grade [odds ratio (OR)=1.709, P=0.009], postoperative anemia (OR=0.983, P=0.011) and excessive intraoperative colloid input (OR=1.55, P=0.037) were identified as risk factors for unplanned reoperation. Propensity score matching was applied, and the difference of unplanned reoperation incidence between the matched groups was statistically significant (14.59% versus 8.54%; P=0.025). The multivariate analyses after propensity score matching confirmed that the intraoperative rate of colloid infusion of more than 2.3 mL/kg/h (OR=1.756, P=0.042) and prior radiotherapy (OR=2.78, P=0.001) are independent risk factors for unplanned reoperation. CONCLUSION: High intraoperative colloid infusion rate and prior radiotherapy may increase the risk of unplanned reoperation in patients who underwent OSCC surgery and vascularized free flap reconstruction.
Assuntos
Carcinoma de Células Escamosas , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Reoperação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Surgical resection of the primary lesion and reconstruction of the defects with free flaps are common treatments for head and neck cancer (HNC). However, various variables can lead to prolonged length of stay (LOS). The aim of this study is to investigate risk factors correlated with prolonged LOS following free flap reconstruction of head and neck defects. METHODS: A retrospective study of patients with all types of free flaps reconstruction of HNC between January 2011 and January 2019 at Sun Yat-sen Memorial Hospital was performed. We recorded predictive variables and divided them into: personal and clinical, hemodynamic, anesthetic and surgical. The primary endpoint was prolonged length of stay. Univariate and multivariate analyses were applied to identify risk factors that associated with prolonged LOS. Propensity score matching was performed with the identified risk variables and other perioperative factors that may impact transfusion decision to explore the independent influence of intraoperative blood transfusion on prolonged LOS. RESULTS: A total of 1047 patients were included in this study. The median LOS was 13.00 (11.00, 16.00) days. Multivariate analysis suggested that blood transfusion, duration of surgery, postoperative complications and unplanned reoperation were associated with prolonged LOS. After propensity score matching, unnecessary blood transfusion and inadequate fluid rate over 24 h, postoperative complications and unplanned reoperation were identified risk factors that led to prolonged LOS. CONCLUSION: Unnecessary blood transfusion and inadequate fluid infusion rate over 24 h were independent risk factors associated with prolonged LOS in HNC patients who underwent free flap reconstruction. Our results indicated consideration of restrictive blood transfusion and adequate fluid infusion over postoperative 24 h in these patients.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Humanos , Retalhos de Tecido Biológico/cirurgia , Tempo de Internação , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND: Free flap reconstruction of head and neck defects is routinely performed with a high success rate nowadays. However, postoperative complications are still commonly observed. The aim of this study is to investigate risk factors correlated with postoperative complications following free flap reconstruction of head and neck defects. METHODS: A retrospective study of all patients undergoing free flap reconstruction of head and neck defects between January 2018 and January 2020 at Sun Yat-sen Memorial Hospita, Guangzhou, China was performed. Preoperative, intraoperative, and postoperative data were collected retrospectively. The primary outcome variables were postoperative complications, which were divided into medical and surgical complications. All patients were grouped by either complications or no complications. Univariate and multivariate logistic regression models were used to identify risk factors predicting complications. RESULTS: 850 patients underwent free flap reconstruction of head and neck defects during the study period (Male: 65.29%; Mean [SD] age: 54.90 [13.78] years). Postoperative complications developed in 125 (14.71%) patients, among which, 101 (11.88%) patients developed surgical complications, 29 (3.41%) patients developed medical complications and 5 (0.59%) patients developed both surgical and medical complications. Total flap necrosis was observed in 11 (1.29%) patients. After multivariate analysis, several risk factors incluing postoperative ICU admission, coronary heart disease, post radiotherapy surgery and flap types were identified correlated with postoperative complications. CONCLUSIONS: Our study identified related variables for a higher risk of postoperative complications development following free flap reconstruction of head and neck defects. Early detection of these risk factors will improve prognosis.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Pessoa de Meia-Idade , Retalhos de Tecido Biológico/efeitos adversos , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: This study aimed to identify risk factors that were associated with mandatory intensive care unit (ICU) admission after gastrectomy for gastric cancer. We then employed these risk factors to construct and validate a nomogram for predicting mandatory ICU admission after gastrectomy, which may identify those who require ICU indeed and improve ICU utilization. METHODS: A number of 999 gastric cancer patients undergoing gastrectomy from January 2010 to June 2019 were included in the retrospective study. Forty-three patients were classified into mandatory ICU admission groups, and the remaining 956 patients were allocated into the no need for ICU admission group. The candidate variables, including patient demographic characteristics, preoperative laboratory tests and surgical variables, were compared between the two groups. We then carried out univariate and multivariate logistic regression analyses to find out risk factors for mandatory ICU admission. In order to develop the predictive model, we used Akaike information criterion (AIC) to select risk factors via a step-down backward process from the multivariate regression model. RESULTS: A number of risk factors for mandatory ICU admission were identified and subsequently used to build the nomogram: age [odds ratio (OR), 1.03; 95% CI, 1.00-1.07; P=0.031], ASA status (III-IV vs. I-II: OR,1.74; 95% CI, 0.88-3.46; P=0.114), tumor size (OR, 1.28; 95% CI, 1.08-1.51; P=0.004), estimated blood loss (OR, 1.001; 95% CI, 1.000-1.001; P=0.082) as well as intraoperative transfusion (Yes vs. No: OR, 3.82; 95% CI, 1.87-7.82; P<0.001). C-index of the nomogram was 0.800, indicating good discrimination. Both Calibration curve and Hosmer-Lemeshow goodness-of-fit tests (P=0.128) showed that there was a high degree of agreement between the prediction and actual outcome. CONCLUSIONS: A nomogram to predict mandatory ICU admission after gastrectomy for gastric cancer was constructed and validated. Clinicians could apply this predictive model to improve usage of limited ICU resources effectively.
Assuntos
Nomogramas , Neoplasias Gástricas , Gastrectomia , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
PURPOSE: Studies have demonstrated that low serum albumin levels are associated with a high postoperative complication rate after microvascular free flap reconstruction. The aim of this study was to investigate whether perioperative albumin supplementation reduced the postoperative complications of microvascular free flap reconstruction in oral and maxillofacial tumor resections. PATIENTS AND METHODS: Patients who underwent microvascular free flap reconstruction during oral and maxillofacial tumor resections from January 2012 to December 2017 were enrolled in this retrospective study. The predictor variable was perioperative albumin supplementation. The primary outcome variables were surgery-associated postoperative complications, including local and systemic complications. The secondary outcome variables were the total duration of hospital stay, postoperative ICU admission rate, duration of ICU stay, and mortality during hospitalization. RESULTS: In total, 315 patients met the criteria. Patients with serum albumin supplementation showed a lower rate of surgery-associated local complications (6.5 vs 21.6%) with an adjusted odds ratio (OR) of 0.24 (95% confidence interval (CI), 0.12 to 0.49, P < .001). The average postoperative hospital stay was significantly shortened for patients with albumin supplementation (12.56 ± 4.23 vs 15.34 ± 5.24 days, P < .001). However, albumin supplementation had no effect on systemic complications. CONCLUSIONS: The results of this study suggest that perioperative albumin supplementation is associated with a decreased risk of local complications, shortened hospital stay, and decreased need for crystalloid infusion in patients who underwent oral and maxillofacial tumor resections with microvascular free flap reconstruction.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Albuminas , Suplementos Nutricionais , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
BACKGROUND: The aim of this study was to identify a preoperative inflammatory marker with the most predictive value for postoperative complications after pancreaticoduodenectomy (PD). We then combined it with other perioperative variables to construct and validate a nomogram for complications after PD. METHODS: A total of 223 patients who received PD from January 2014 to July 2019 at a high-volume (>60 PDs/year) pancreatic centers in China were included in this retrospective study. All of the PDs were performed by the same surgeon who is beyond the learning curve with more than 100 PDs over the previous 3 years before 2014. 15 preoperative inflammatory markers were collected, including neutrophils, lymphocytes, high-sensitivity C-reactive protein and lactic dehydrogenase. The inflammatory markers' predicting abilities for complications were analyzed by calculating the values of an area under the curve (AUC). The complications included surgical complications (such as pancreatic fistula, delayed gastric emptying and bile leakage) and medical complications (such as sepsis, pneumonia, urinary tract infection, acute heart failure and acute liver failure) in this study. Univariable and multivariable logistic regression analyses were performed to investigate the perioperative features for independent risk factors for complications after PD. Nomograms with or without the most predictive inflammatory for complications were subsequently developed based on multivariable logistic regression using Akaike information criterion. Nomograms' performance was quantiï¬ed and compared in terms of calibration and discrimination. We studied the utility of the nomograms using decision curve analysis. RESULTS: The albumin/ NLR score (ANS) exhibited the highest AUC value (0.616) for predicting postoperative complications. ANS and approach method were identified as independent risk factors for complications. The nomogram with ANS had higher C-index (0.725) and better calibration. The NRI compared between nomograms was 0.160 (95% CI: 0.023-0.296; P=0.022). By decision curve analysis, the model with ANS had higher clinical value. CONCLUSIONS: The ANS is a useful predictor and an independent risk factor for postoperative complications after PD. The nomogram with ANS was constructed with better performance and more clinical beneï¬t for predicting postoperative complications.
RESUMO
Porcine circovirus type 4 (PCV4), a novel circovirus, was identified in pigs with serious symptoms, including porcine dermatitis and nephropathy syndrome (PDNS)-like signs, in China in 2019. This study investigated the prevalence and genome diversity of PCV4 in pigs from Guangxi Province, China, between 2015 and 2019. Thirteen of 257 (5.1%) samples were positive for PCV4, 9 of these (69.2%) PCV4-positive samples were coinfected with PCV2 or PCV3, and one PCV4-positive sample was coinfected with both PCV2 and PCV3. Three complete PCV4 genomes shared 36.9-73.8% nucleotide similarity with other representative circovirus genomes. Phylogenetic analysis indicated that PCV4 was most closely related to bat-associated circovirus and mink circovirus. In summary, this is the first epidemiological investigation and evolutionary analysis of PCV4 in Guangxi Province, China, and the results provide insight into the molecular epidemiology of PCV4.
Assuntos
Infecções por Circoviridae/genética , Circovirus/genética , Filogenia , Doenças dos Suínos/genética , Animais , Proteínas do Capsídeo/genética , China/epidemiologia , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/patologia , Infecções por Circoviridae/veterinária , Circovirus/patogenicidade , Genoma Viral/genética , Humanos , Suínos/genética , Suínos/virologia , Doenças dos Suínos/epidemiologia , Proteínas Virais/genéticaRESUMO
Considering the fact that melatonin acts as protective agent in various cognitive impairment, we decided to explore the precise effect of pretreatment with melatonin on cognitive function, mitochondrial activity, apoptosis and synaptic integrity in aged rats anesthetized by propofol. We first randomly allocated the thirty Sprague Dawley rats into three groups: Control vehicle-treated group (Con), Propofol-treated group (Pro) and Melatonin + Propofol group (Mel + Pro). The Barnes maze, open field and contextual fear conditioning test were employed to evaluate spatial memory, exploratory behavior and general locomotor activity, and hippocampus-dependent learning and memory ability, respectively. Moreover, mitochondrial function (including reactive oxygen species, mitochondrial membrane potential and ATP levels) and apoptosis were detected in the regions of hippocampus (HIP) and prefrontal cortex (PFC). The results of behavioral tests suggested that melatonin improved propofol-induced memory impairment in aged rats. Melatonin mitigated mitochondrial dysfunction and decreased the apoptotic cell counts in the regions of HIP and PFC. Furthermore, prophylactic melatonin treatment also reversed the propofol-induced inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction. On the whole, our results indicated that melatonin ameliorated the propofol-induced cognitive disorders via attenuating mitochondrial dysfunction, apoptosis, inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction.
Assuntos
Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Melatonina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Propofol/toxicidade , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Células Cultivadas , Hipocampo/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
KEY POINTS: Spinal cord dorsal horn srGAP3 (slit-robo GTPase activating protein 3) increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity, which can be reduced by srGAP3, decreases in the initiation phase and increases in the maintenance phase. The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain. Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain. SrGAP3 small interfering RNA can ameliorate neuropathic pain only when administrated in the initiation phase. The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase. Combined targeting of srGAP3 in the initiation phase and Rac1 in the maintenance phase can produce optimal analgesic efficacy. ABSTRACT: Neuropathic pain includes an initiation phase and maintenance phase, each with different pathophysiological processes. Understanding the synaptic plasticity and molecular events in these two phases is relevant to exploring precise treatment strategies for neuropathic pain. In the present study, we show that dendritic spine density increases in the spinal dorsal horn in the initiation phase of neuropathic pain induced by paclitaxel and that the spine maturity ratio increases in the maintenance phase. Increased srGAP3 (slit-robo GTPase activating protein 3) facilitates dendritic spine sprouting in the initiation phase. In the maintenance phase, srGAP3 decreases to upregulate Rac1 activity, which facilitates actin polymerization and dendritic spine maturation and thus the persistence of neuropathic pain. Knockdown of srGAP3 in the initiation phase or inhibition of Rac1 in the maintenance phase attenuates neuropathic pain. Combined intervention of srGAP3 in the initiation phase, and Rac1 in the maintenance phase shows better analgesic efficacy against neuropathic pain. The present study demonstrates the role of srGAP3-Rac1 in dendritic spine plasticity in the two phases of neuropathic pain and, accordingly, provides treatment strategies for different phases of neuropathic pain.
Assuntos
Espinhas Dendríticas , Neuralgia , Animais , Espinhas Dendríticas/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Manutenção , Neuralgia/tratamento farmacológico , Paclitaxel/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
Porcine circovirus type 3 (PCV3) is an emerging circovirus species associated with several diseases. The study aimed to investigate the frequency of porcine circovirus 3 (PCV3) and its coinfection with canine parvovirus type 2 (CPV-2) in dogs in the Guangxi province from 2015 to 2017, China, and to examine the genome diversity of PCV3. Using polymerase chain reaction (PCR) amplification and sequencing, 96 of 406 (23.6%)samples were positive for PCV3, 38 out of 406 (9.4%) samples were coinfected with both PCV3 and CPV-2. The CPV-positive rate was significantly higher in the PCV3-positive samples than in the non-PCV3 samples, and the difference was extremely significant (Pâ¯<â¯0.01). The complete genome (n=4) and ten capsid genes (n=10) of PCV3 were sequenced. Multiple sequence alignment results showed that these sequences shared 98.5-100% nucleotide similarity with the reference genome sequence and 97.5-100% nucleotide similarity with the reference capsid gene sequence. PCV3 was classified into two different genotypes, according to phylogenetic analysis based on the whole genome. These strains were clustered in PCV3a, showing a close relationship with PCV3-US/SD2016. Surprisingly, we separately analyzed these PCV3 strains from the Guangxi province and found that the dog and pig PCV3 are from different branches. In summary, this was the first seroprevalence and genetic investigation of PCV3 in dogs in the Guangxi province, China, and the first complete genome PCV3 from dogs obtained in the world. The results provide insights into the epidemiology and pathogenesis of this important virus.