Inhibition of spinal BRD4 alleviates pyroptosis and M1 microglia polarization via STING-IRF3 pathway in morphine-tolerant rats.

BACKGROUND: Morphine tolerance has been a challenging medical issue. Neuroinflammation is considered as a critical mechanism for the development of morphine tolerance. Bromodomain-containing protein 4 (BRD4), a key regulator in cell damage and inflammation, participates in the development of chronic pain. However, whether BRD4 is involved in morphine tolerance and the underlying mechanisms remain unknown. METHODS: The morphine-tolerant rat model was established by intrathecal administration of morphine twice daily for 7 days. Behavior test was assessed by a tail-flick latency test. The roles of BRD4, pyroptosis, microglia polarization and related signaling pathways in morphine tolerance were elucidated by Western blot, real-time quantitative polymerase chain reaction, and immunofluorescence. RESULTS: Repeated morphine administration upregulated BRD4 level, induced pyroptosis, and promoted microglia M1-polarization in spinal cord, accompanied by the release of proinflammatory cytokines, such as TNF-α and IL-1ß. JQ-1, a BRD4 antagonist, alleviated the development of morphine tolerance, diminished pyroptosis and induced the switch of microglia from M1 to M2 phenotype. Mechanistically, stimulator of interferon gene (STING)- interferon regulatory factor 3 (IRF3) pathway was activated and the protective effect of JQ-1 against morphine tolerance was at least partially mediated by inhibition of STING-IRF3 pathway. CONCLUSION: This study demonstrated for the first time that spinal BRD4 contributes to pyroptosis and switch of microglia polarization via STING-IRF3 signaling pathway during the development of morphine tolerance, which extend the understanding of the neuroinflammation mechanism of morphine tolerance and provide an alternative strategy for the precaution against of this medical condition.

Interleukin-18 in chronic pain: Focus on pathogenic mechanisms and potential therapeutic targets.

Chronic pain has been proven to be an independent disease, other than an accompanying symptom of certain diseases. Interleukin-18 (IL-18), a pro-inflammatory cytokine with pleiotropic biological effects, participates in immune modulation, inflammatory response, tumor growth, as well as the process of chronic pain. Compelling evidence suggests that IL-18 is upregulated in the occurrence of chronic pain. Antagonism or inhibition of IL-18 expression can alleviate the occurrence and development of chronic pain. And IL-18 is located in microglia, while IL-18R is mostly located in astrocytes in the spinal cord. This indicates that the interaction between microglia and astrocytes mediated by the IL-18/IL-18R axis is involved in the occurrence of chronic pain. In this review, we described the role and mechanism of IL-18 in different types of chronic pain. This review provides strong evidence that IL-18 is a potential therapeutic target in pain management.

Clinical characteristics and prognosis of pediatric Listeria monocytogenes meningitis based on 10-year data from a large children's hospital in China.

This study aims to summarize the clinical characteristics and prognosis of Listeria monocytogenes (LM) meningitis in children in Chongqing, China. A retrospective analysis of the clinical data and follow-up results of 20 LM meningitis patients admitted to the Children's Hospital of Chongqing Medical University (CHCMU) from January 2012 to December 2022 was performed. The LM meningitis incidence rate was between 0 and 14.3 per 100,000 persons. The median age at onset was 8.98 months. There were five neonate cases, which all had perinatal abnormalities. Seven non-neonatal cases (7/15, 46.7%) had a documented history of contaminated food intake. One case had primary immunodeficiency. The most common symptoms were fever (20/20), altered consciousness (19/20), and vomiting (15/20). Seven cases had seizures, eight cases had cranial nerve involvement, eight cases had positive Babinski sign, and 10 cases had positive meningeal signs. The most common complications were hyponatremia (6/20), hypokalemia (6/20), respiratory failure (5/20), subdural effusion (3/20), and hydrocephalus (2/20). Treatment primarily involved monotherapy or combination therapy with meropenem (15/20) and ampicillin (10/20). Fifteen cases were treated with monotherapy or combination therapy using vancomycin. Twelve cases were successfully followed up from 10 months to 9 years and 6 months, and all had favorable long-term outcomes. LM meningitis incidence in children is low and with nonspecific clinical manifestations. Strengthening food hygiene and safety education, and avoiding infections during pregnancy are important to prevent LM infection in neonates and high-risk individuals. Meropenem and ampicillin are the preferred treatments. Early diagnosis and treatment can improve prognosis.IMPORTANCEThe incidence of LM meningitis is extremely low, and there is currently no standardized treatment. We conducted a retrospective analysis of ten years of data from CHCMU regarding diagnosed LM meningitis cases, aiming to provide clinical evidence for the diagnosis and treatment.

The metabolism of nonstructural carbohydrates, lipids, and energy in two Cycas species with differential tolerance to unexpected freezing stress.

Introduction: With the climate warming, the occurrence of freezing events is projected to increase in late spring and early autumn in the Northern Hemisphere. Observation of morphological traits showed that Cycas panzhihuaensis was more tolerant to unexpected freezing stress than C. bifida. Energy balance is crucial for plant tolerance to stress. Here, we aimed to determine whether the different responses of the two species to the unpredicted freezing stress were associated with the metabolism of energy and related substances. Methods: The effects of unexpected freezing temperatures on C. panzhihuaensis and C. bifida were studied by measuring chlorophyll fluorescence parameters, energy charge and the profile of nonstructural carbohydrates (NSC) and lipids. Results: C. panzhihuaensis exhibited higher stability of photosynthetic machinery than C. bifida under unpredicted freezing events. Significant interaction between species and treatments were observed in the energy charge, the level of NSC and its most components and the amount of most lipid categories and lipid classes. The decrease of soluble sugar and the increase of neutral glycerolipids at the early freezing stage, the accumulation of membrane glycerolipids at the late freezing stage and the continuous decrease of energy charge during the freezing period were the characteristics of C. panzhihuaensis responding to unexpected freezing stress. The degradation of membrane glycerolipids and the continuous decrease of soluble sugar during the freezing period and the accumulation of neutral glycerolipids and energy charge at the late freezing stage represented the characteristics of C. bifida responses. Discussion: The different freezing sensitivity between C. panzhihuaensis and C. bifida might be associated with the differential patterns of the metabolism of energy, NSC and lipids. C. panzhihuaensis possesses the potential to be introduced to the areas of higher latitudes and altitudes.

Missing data imputation, prediction, and feature selection in diagnosis of vaginal prolapse.

BACKGROUND: Data loss often occurs in the collection of clinical data. Directly discarding the incomplete sample may lead to low accuracy of medical diagnosis. A suitable data imputation method can help researchers make better use of valuable medical data. METHODS: In this paper, five popular imputation methods including mean imputation, expectation-maximization (EM) imputation, K-nearest neighbors (KNN) imputation, denoising autoencoders (DAE) and generative adversarial imputation nets (GAIN) are employed on an incomplete clinical data with 28,274 cases for vaginal prolapse prediction. A comprehensive comparison study for the performance of these methods has been conducted through certain classification criteria. It is shown that the prediction accuracy can be greatly improved by using the imputed data, especially by GAIN. To find out the important risk factors to this disease among a large number of candidate features, three variable selection methods: the least absolute shrinkage and selection operator (LASSO), the smoothly clipped absolute deviation (SCAD) and the broken adaptive ridge (BAR) are implemented in logistic regression for feature selection on the imputed datasets. In pursuit of our primary objective, which is accurate diagnosis, we employed diagnostic accuracy (classification accuracy) as a pivotal metric to assess both imputation and feature selection techniques. This assessment encompassed seven classifiers (logistic regression (LR) classifier, random forest (RF) classifier, support machine classifier (SVC), extreme gradient boosting (XGBoost) , LASSO classifier, SCAD classifier and Elastic Net classifier)enhancing the comprehensiveness of our evaluation. RESULTS: The proposed framework imputation-variable selection-prediction is quite suitable to the collected vaginal prolapse datasets. It is observed that the original dataset is well imputed by GAIN first, and then 9 most significant features were selected using BAR from the original 67 features in GAIN imputed dataset, with only negligible loss in model prediction. BAR is superior to the other two variable selection methods in our tests. CONCLUDES: Overall, combining the imputation, classification and variable selection, we achieve good interpretability while maintaining high accuracy in computer-aided medical diagnosis.

Complexity-based graph convolutional neural network for epilepsy diagnosis in normal, acute, and chronic stages.

Introduction: The automatic precision detection technology based on electroencephalography (EEG) is essential in epilepsy studies. It can provide objective proof for epilepsy diagnosis, treatment, and evaluation, thus helping doctors improve treatment efficiency. At present, the normal and acute phases of epilepsy can be well identified through EEG analysis, but distinguishing between the normal and chronic phases is still tricky. Methods: In this paper, five popular complexity indicators of EEG signal, including approximate entropy, sample entropy, permutation entropy, fuzzy entropy and Kolmogorov complexity, are computed from rat hippocampi to characterize the normal, acute, and chronic phases during epileptogenesis. Results of one-way ANOVA and principal component analysis both show that utilizing complexity features, we are able to easily identify differences between normal, acute, and chronic phases. We also propose an innovative framework for epilepsy detection based on graph convolutional neural network (GCNN) using multi-channel EEG complexity as input. Results: Combining information of five complexity measures at eight channels, our GCNN model demonstrate superior ability in recognizing the normal, acute, and chronic phases. Experiments results show that our GCNN model reached the high prediction accuracy above 98% and F1 score above 97% among these three phases for each individual rat. Discussion: Our research practice based on real data shows that EEG complexity characteristics are of great significance for recognizing different stages of epilepsy.

Clinical Features and a Prediction Nomogram for Prognosis in Children with Escherichia coli Meningitis.

BACKGROUND: We aimed to build a prediction nomogram for early prediction of poor prognosis in children with Escherichia coli meningitis and analyzed the course of treatment and discharge criteria. METHODS: Eighty-seven pediatric patients with E coli meningitis were retrospectively recruited from the Children's Hospital of Chongqing Medical University between June 2012 and November 2021. Univariate analysis and binary logistic analysis were used to evaluate the risk factors, and the prediction model was built. RESULTS: E coli meningitis is more common in children <3 months old in our study (86.2%). Common complications were subdural effusion (39.1%), followed by hydrocephalus (13.8%) and repeated convulsions (12.6%). The mortality rate and sequelae rate of E coli meningitis in children was ∼10.9% and ∼6.3%, respectively. Univariate analysis showed that 13 clinical indicators were associated with poor prognosis of E coli meningitis in children. In binary logistic analysis, risk factors were seizures (P = .032) and the last cerebrospinal fluid glucose content before discharge (P = .002). A graphical nomogram was designed. The area under the receiver operating characteristic curve was 0.913. The Hosmer-Lemeshow test showed that the model was a good fit (P = .648). Internal validation proved the reliability of the prediction nomogram. CONCLUSIONS: E coli meningitis is more common in children <3 months old in our study. The rate of complications and sequelae are high. The prediction nomogram could be used to assess the risk of poor prognosis in children with E coli meningitis by clinicians.

Spatially Modulated Fiber Speckle for High-Sensitivity Refractive Index Sensing.

A fiber speckle sensor (FSS) based on a tapered multimode fiber (TMMF) has been developed to measure liquid analyte refractive index (RI) in this work. By the lateral and axial offset of input light into TMMF, several high-order modes are excited in TMMF, and the speckle pattern is spatially modulated, which affects an asymmetrical speckle pattern with a random intensity distribution at the output of TMMF. When the TMMF is immersed in the liquid analyte with RI variation, it influences the guided modes, as well as the mode interference, in TMMF. A digital image correlations method with zero-mean normalized cross-correlation coefficient is explored to digitize the speckle image differences, analyzing the RI variation. It is found that the lateral- and axial-offsets-induced speckle sensor can enhance the RI sensitivity from 6.41 to 19.52 RIU-1 compared to the one without offset. The developed TMMF speckle sensor shows an RI resolution of 5.84 × 10-5 over a linear response range of 1.3164 to 1.3588 at 1550 nm. The experimental results indicate the FSS provides a simple, efficient, and economic approach to RI sensing, which exhibits an enormous potential in the image-based ocean-sensing application.

Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.

BACKGROUND AND PURPOSE: Morphine is amongst the most effective analgesics available for the management of severe pain. However, prolonged morphine treatment leads to analgesic tolerance which limits its clinical usage. Previous studies have demonstrated that melatonin ameliorates morphine tolerance by reducing neuroinflammation. However, little is known about the relationship between Toll like receptor 2 (TLR2) and neuroinflammation in morphine tolerance. The aim of this study was to explore the role of TLR2 in morphine tolerance and its connections with melatonin and Nod-like receptor protein 3 (NLRP3) inflammasome. METHODS: Sprague-Dawley rats were treated with morphine for 7 days and tail-flick latency test was performed to identify the induction of analgesic tolerance. The roles of TLR2 in microglia activation and morphine tolerance were assessed pharmacologically, and the possible interactions between melatonin, TLR2 and NLRP3 inflammasome were investigated. KEY RESULTS: Morphine tolerance was accompanied by increased TLR2 expression and NLRP3 inflammasome activation in spinal cord. whereas melatonin level was down-regulated. Chronic melatonin administration resulted in a reduced TLR2 expression and NLRP3 inflammasome activation. Moreover, the analgesic effect of morphine was partially restored. Inhibition of TLR2 suppressed the microglia and NLRP3 inflammasome activation, as well as restored the spinal melatonin level while attenuated the development of morphine tolerance. Furthermore, the inhibition of microglia activation ameliorated morphine tolerance via inhibiting TLR2-NLRP3 inflammasome signaling in spinal cord. CONCLUSION: In this study, we directly demonstrate a TLR2-melatonin negative feedback loop regulating microglia and NLRP3 inflammasome activation during the development of morphine tolerance.

The prospective study of 54 children with electrical status epilepticus during sleep: How to simplify the electroencephalogram diagnosis and guide the treatment.

OBJECTIVE: To simplify the electroencephalogram (EEG) diagnosis and guide the treatment of electrical status epilepticus during sleep (ESES). METHODS: We recruited 54 children with ESES from December 2019 to December 2020 and compared various spike-wave index (SWI) calculation methods. Time-frequency analysis assessed the correlation between high-frequency oscillations energy and the SWI. We divided 42 children into responder and non-responder treatment groups based on the observations made during a 12-month follow-up period and evaluate different treatment and the independent risk factors of refractory ESES. RESULTS: The SWI of 5 min before the second sleep cycle of non-rapid eye movement (NREM; long method II) and that of all NREM sleep (total method) were not significantly different (p = .06). The average energy of γ (r = .288, p = .002) and ripple (r = .203, p = .04) oscillations were correlated with the SWI. Multivariable logistic regression analysis showed that encephalomalacia was an independent risk factor for refractory ESES (OR: 10.48, 95% CI: 1.62-67.63). The clinical seizure improvement rates of anti-seizure medications (ASMs), ASMs with benzodiazepines, and ASMs with benzodiazepines and steroids after 12 months were 9.3%, 42.8%, and 53.8%, EEG improvement rate were 5.5%, 30.9% and 37%, respectively. The intelligence of the children in the responder treatment group has improved during the 1-year follow-up. SIGNIFICANCE: These findings demonstrate EEG and clinical features of ESES and may provide basis for simplifying diagnosis and guiding the treatment of children with ESES.

Hyperbaric oxygen and treadmill exercise partially prevented bone loss and bone microarchitecture deterioration in ovariectomized rats.

INTRODUCTION: Previous studies have demonstrated the beneficial effects of treadmill exercise (EX) on osteoporosis, and of hyperbaric oxygen (HBO) on osteoblast and osteoclast formation in vitro. We investigated the effects of HBO and the combination of HBO and EX on osteoporosis in ovariectomized rats. METHODS: Forty 3-month-old female Sprague-Dawley rats were randomly divided into 5 groups (n = 8): a sham control group (Control); an ovariectomy group; an ovariectomy with treadmill exercise treatment group; an ovariectomy with HBO treatment group; and an ovariectomy with HBO treatment combined with treadmill exercise group. The HBO exposures were 203 kPa, 85-90% O2, 90 min and the exercise regimen was 20 m·min⁻¹, 40 min·day¹, 5° slope. Both treatments were administered once daily, five days a week for 12 weeks until the rats were sacrificed. RESULTS: All three treatments (HBO, exercise, and both combined) significantly promoted the expression of the osteoblast-related gene and oxidative metabolism-related gene (PGC-1α). They also exerted significant inhibitory effects on the osteoclast-related mRNA expression (RANKL) and bone resorption marker CTX-I. Additionally, exercise and the combination exercise-HBO treatment increased serum superoxide dysmutase (SOD) and sclerostin expression. No significant between-group difference was observed. CONCLUSIONS: Hyperbaric oxygen, exercise, and the combination ameliorated bone microarchitecture deterioration and ovariectomy-induced bone loss in rats, and these inhibitory effects may be associated with the increased SOD and up-regulated PGC-1α.

Chiral photonic topological states in Penrose quasicrystals.

Electromagnetic topological edge states typically are created in photonic systems with crystalline symmetry and these states emerge because of the topological feature of bulk Bloch bands in momentum space according to the bulk-edge correspondence principle. In this work, we demonstrate the existence of chiral topological electromagnetic edge states in Penrose-tiled photonic quasicrystals made of magneto-optical materials, without relying on the concept of bulk Bloch bands in momentum space. Despite the absence of bulk Bloch bands, which naturally defiles the conventional definition of topological invariants in momentum space characterizing these states, such as the Chern number, we show that some bandgaps in these photonic quasicrystals still could host unidirectional topological electromagnetic edge states immune to backscattering in both cylinders-in-air and holes-in-slab configurations. Employing a real-space topological invariant based on the Bott index, our calculations reveal that the bandgaps hosting these chiral topological edge states possess a nontrivial Bott index of ±1, depending on the direction of the external magnetic field. Our work opens the door to the study of topological states in photonic quasicrystals.

Risk Factors of Perioperative Brain Injury in Children Under Two Years Undergoing Coarctation Repair.

BACKGROUND: To investigate clinical manifestations and factors of perioperative brain injury (PBI) after surgical repair of coarctation of the aorta (CoA) combined with other heart malformations under cardiopulmonary bypass (CPB) in children under two years. METHODS: The clinical data of 100 children undergoing CoA repair were retrospectively reviewed between January 2010 and September 2021. Univariate and multivariate analyses were performed to identify factors of PBI development. Hierarchical and K-means cluster analyses were conducted to evaluate the association between hemodynamic instability and PBI. RESULTS: Eight children developed postoperative complications, and all of them had a favorable neurological outcome one year after surgery. Univariate analysis revealed eight risk factors associated with PBI. Multivariate analysis indicated operation duration (P = 0.04, odds ratio [OR], 2.93; 95% confidence interval [CI], 1.04 to 8.28) and pulse pressure (PP) minimum (P = 0.01; OR, 0.22; 95% CI, 0.06 to 0.76) were independently associated with PBI. The following three parameters emerged for cluster analysis: PP minimum, mean arterial pressure (MAP) dispersion, and systemic vascular resistance (SVR) average. Using cluster analysis, PBI mainly occurred in subgroups 1 (12%, three of 26) and 2 (10%, five of 48). The mean value of PP and MAP in subgroup 1 was significantly higher than in subgroup 2. The mean SVR in subgroup 1 was the highest. The lowest PP minimum, MAP, and SVR were observed in subgroup 2. CONCLUSION: Lower PP minimum and longer operation duration were independent risk factors for developing PBI in children under two years during CoA repair. Unstable hemodynamics should be avoided during CPB.

The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population.

BACKGROUND: Subthreshold depression could be a significant precursor to and a risk factor for major depression. However, reliable estimates of the prevalence and its contribution to developing major depression under different terminologies depicting subthreshold depression have to be established. METHODS: By searching PubMed and Web of Science using predefined inclusion criteria, we included 1 129 969 individuals from 113 studies conducted. The prevalence estimates were calculated using the random effect model. The incidence risk ratio (IRR) was estimated by measuring the ratio of individuals with subthreshold depression who developed major depression compared to that of non-depressed individuals from 19 studies (88, 882 individuals). RESULTS: No significant difference in the prevalence among the different terminologies depicting subthreshold depression (Q = 1.96, p = 0.5801) was found. By pooling the prevalence estimates of subthreshold depression in 113 studies, we obtained a summary prevalence of 11.02% [95% confidence interval (CI) 9.78-12.33%]. The youth group had the highest prevalence (14.17%, 95% CI 8.82-20.55%), followed by the elderly group (12.95%, 95% CI 11.41-14.58%) and the adult group (8.92%, 95% CI 7.51-10.45%). Further analysis of 19 studies' incidence rates showed individuals with subthreshold depression had an increased risk of developing major depression (IRR = 2.95, 95% CI 2.33-3.73), and the term minor depression showed the highest IRR compared with other terms (IRR = 3.97, 95% CI 3.17-4.96). CONCLUSIONS: Depression could be a spectrum disorder, with subthreshold depression being a significant precursor to and a risk factor for major depression. Proactive management of subthreshold depression could be effective for managing the increasing prevalence of major depression.

Developmental characteristics of visual evoked potentials to different stimulation in normal children.

OBJECTIVE: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy children. METHODS: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP. RESULTS: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision. CONCLUSION: FVEP can be evoked in normal children at less than 2 Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.

Risk factors and a predictive model for the development of epilepsy after Japanese encephalitis.

BACKGROUND: We aimed to study seizure characteristics during the acute phase of Japanese encephalitis (JE) in children, determine the risk factors of postencephalitic epilepsy (PEE), establish a risk prediction model for the disease, and construct a nomogram to visualize the model. METHODS: We retrospectively analyzed the clinical data and follow-up results of 328 children with JE who were hospitalized between January 2011 and December 2020. Risk factors were screened using univariable analysis, a predictive model was built using binary logistic analysis, lasso regression was used for variable screening, and a nomogram was developed. RESULTS: Of the 328 children with JE enrolled in the study, 216 (65.9%, 216/328) had seizures in the acute phase. The incidence of PEE was 14.7% (39/264), The cumulative percentages of PEE after discharge was 10.6% (28/264)at 6 months, which increased to 13.6%(36/264)at 3 years. 38.5% of patients with PEE had generalized onset seizures, and 17.9% had focal motor seizures. Univariable analysis revealed that 22 clinical indicators were related to the PPE; Multivariable analysis identified seizure number >5 (OR (95%CI) = 3.013 (1.046-8.676), P = 0.041), status epilepticus (OR (95%CI) = 3.918 (1.212-12.669), P = 0.023), and Coma (OR (95%CI) = 22.495 (8.686-58.285), P<0.001) as independent risk factors for PEE. The risk prediction model: ln(p/1p)= -3.533 + 1.103 × (seizures number > 5) +1.366 × (status epilepticus) + 3.113 × (Coma) was developed, and a nomogram was constructed. The area under the ROC curve (AUC), calibration plot, and Hosmer-Lemeshow test showed that the model had good discrimination and calibration. Ordinary bootstrapping was used for internal validation, and the predictive results of the original and test sets were consistent. CONCLUSIONS: Seizure is a common manifestation during acute encephalitis and sequelae in children with JE. The nomogram constructed in this study could be used for early prediction, and could facilitate early intervention.

Oxidative stress responses in two marine diatoms during acute n-butyl acrylate exposure and the toxicological evaluation with the IBRv2 index.

n-Butyl acrylate (nBA), a typical hazardous and noxious substance (HNS), is the largest-volume acrylate ester used to produce various types of polymers. With the increasing volume of nBA subject to maritime transportation, its accidental leakage poses a great risk to the marine organisms. Therefore, it is necessary to evaluate the ecological risk of nBA in marine environments. In this study, two species of marine microalgae, Skeletonema costatum and Phaeodactylum tricornutum, were used to explore the toxic effects of nBA based on their growth, pigment content, and oxidative stress. The growth of each species was significantly inhibited by nBA, showing a 96 h-EC50 value of 2.23 mg/L for P. tricornutum and 8.19 mg/L for S. costatum, respectively. Although chlorophylls a and c exerted a hormesis effect in P. tricornutum, contents of pigments generally decreased at high concentrations. In P. tricornutum, all detected antioxidants (reduced glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) were stimulated at concentrations ranging from 1.50 to 3.82 mg/L. However, these elevations were not enough to reduce the oxidative damage caused by nBA, because the content of malondialdehyde (MDA) increased continuously during 96-h exposure. For S. costatum, the activities of only two antioxidants (GSH and CAT) were enhanced, which is enough to prevent the MDA content from rising, even at higher concentrations of nBA (5-10 mg/L). The Integrated Biomarker Response Version 2 (IBRv2) index that combines responses of the above five oxidative stress biomarkers, was not only correlated positively with nBA concentration but could also indicate the occurrence of oxidative stress caused by acute concentration of nBA. These findings showed that P. tricornutum was sensitive to nBA compared to S. costatum, and the IBRv2 index was an effective tool for evaluating ecotoxicological effects on marine microalgae due to nBA spills.

A Nomogram to Predict Bacterial Meningitis-associated Hydrocephalus: A Single-Center Retrospective Study.

OBJECTIVE: We aimed to develop a predictive nomogram for the early detection of hydrocephalus in children with bacterial meningitis. METHODS: This retrospective study was based on data of children with bacterial meningitis admitted to our hospital between January 2016 and December 2020. Risk factors were evaluated using univariate analysis, and the predictive model/nomogram was built using binary logistic analysis. A nomogram calibration plot, Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve evaluated the predictive performance. Ordinary bootstrapping processed the internal validation. RESULTS: We enrolled 283 patients who matched the inclusion criteria, among whom 41 cases (14.49%) had confirmed bacterial meningitis-associated hydrocephalus (BMAH). The incidence of sequelae in the patients with BMAH was 88.9% (24/27), which was significantly higher than that in the patients without BMAH. Univariate regression analysis revealed that 14 clinical indicators were associated with BMAH. Multivariate analysis identified 4 variables as independent risk factors to establish the predictive model: repeated seizures, loss of consciousness, procalcitonin ≥7.5 ng/dL and mechanical ventilation. And a graphical nomogram was designed. The area under the ROC curve was 0.910. In the Hosmer-Lemeshow test the P value was 0.610. The mean absolute error in the calibration plot was 0.02. Internal validation showed the testing set was in good accordance with the original set when internal validation was performed. CONCLUSIONS: The predictive model/nomogram of BMAH could be used by clinicians to determine hydrocephalus risk.

A Response Surface Analysis of the Combination of Dexmedetomidine and Sufentanil for Attenuating the Haemodynamic Response to Endotracheal Intubation.

Purpose: Dexmedetomidine combined with opioids has been extensively used to blunt cardiovascular responses to endotracheal intubation. To determine their interaction, we aimed to develop a response surface model between dexmedetomidine and sufentanil. Methods: One hundred and twenty patients undergoing scheduled gynaecological surgery were recruited. According to a simulation of slice design, patients received different dose pairs of dexmedetomidine (0 to 1.1 µg/kg) and sufentanil (.1 to .5 µg/kg). The mean arterial blood pressure and heart rate of patients were recorded just before endotracheal intubation, immediately after intubation, and during the first 3 min after intubation. The primary outcomes were haemodynamic changes. The full dose-response relationship between dexmedetomidine and sufentanil was analysed using a logit model. Results: This response surface model revealed that the interaction between dexmedetomidine and sufentanil was additive. The dose pairs that could effectively attenuate the haemodynamic response to endotracheal intubation primarily ranged from .3 to .4 µg/kg and .5 to 1.1 µg/kg for sufentanil and dexmedetomidine, respectively. Conclusion: When used propofol as the main hypnotic drug during anaesthesia induction, dexmedetomidine could effectively reduce the requirement of sufentanil in an additive manner. However, it is not an effective drug for ablating the cardiovascular response to endotracheal intubation when used alone. The clinical trial registry. The trial registry name: Chinese Clinical Trial Registry. Registration number: ChiCTR1800015273. URL:http://www.chictr.org.cn.

Clinical features and prognostic analysis of posterior reversible encephalopathy syndrome in children.

BACKGROUND: We aimed to investigate the clinical features and prognosis of posterior reversible encephalopathy syndrome (PRES) in children. METHODS: Clinical data of children with PRES diagnosed at the Children's Hospital of Chongqing Medical University from June 2015 to May 2019 were retrospectively analyzed. RESULTS: The study enrolled 47 patients with a mean age at diagnosis of 8.79 ± 3.72 years (range, 2-15 years). PRES causes included renal disorder (29/47), hematological disease (13/47), and hypertension (5/47). PRES manifested as seizure (43/47), headache (28/47), visual impairment (18/47), dizziness (18/47), vomiting (18/47), and mental and behavioral abnormalities (17/47). Forty-six children had hypertension (46/47) at PRES onset. Magnetic resonance imaging (MRI) mainly involved the parietal and occipital lobes (42/47), 38 cases were mild (38/47), seven were moderate (7/47), and two were severe (2/47). The clinical symptoms of 41 patients (41/47) were relieved within 1-2 weeks. Thirty-seven children were followed up for 7-54 months (modified Rankin Scale). Twenty-five children had favorable outcomes (25/37). Twelve children had adverse outcomes (12/37), including epilepsy, disorders of consciousness, visual impairment, and mental decline. Analysis of single factors revealed that severity on MRI, length of in-hospital stay, and mental and behavioral abnormalities were related to adverse outcomes after PRES. Analysis of multiple factors revealed that severity on MRI and length of in-hospital stay were independent risk factors for PRES. CONCLUSION: Pediatric PRES is a clinical radiographic syndrome with multiple etiologies. Most patients have a good prognosis. Severity on MRI and length of in-hospital stay are independent risk factors.