Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

VX-765 Alleviates Circadian Rhythm Disorder in a Rodent Model of Traumatic Brain Injury Plus Hemorrhagic Shock and Resuscitation.

Severe traumatic brain injury (TBI) can result in persistent complications, including circadian rhythm disorder, that substantially affect not only the injured people, but also the mood and social interactions with the family and the community. Pyroptosis in GFAP-positive astrocytes plays a vital role in inflammatory changes post-TBI. We determined whether VX-765, a low molecular weight caspase-1 inhibitor, has potential therapeutic value against astrocytic inflammation and pyroptosis in a rodent model of TBI plus hemorrhagic shock and resuscitation (HSR). A weight-drop plus bleeding and refusion model was used to establish traumatic exposure in rats. VX-765 (50 mg/kg) was injected via the femoral vein after resuscitation. Wheel-running activity was assessed, brain magnetic resonance images were evaluated, the expression of pyroptosis-associated molecules including cleaved caspase-1, gasdermin D (GSDMD), and interleukin-18 (IL-18) in astrocytes in the region of anterior hypothalamus, were explored 30 days post-trauma. VX-765-treated rats had significant improvement in circadian rhythm disorder, decreased mean diffusivity (MD) and mean kurtosis (MK), increased fractional anisotropy (FA), an elevated number and branches of astrocytes, and lower cleaved caspase-1, GSDMD, and IL-18 expression in astrocytes than TBI + HSR-treated rats. These results demonstrated that inhibition of pyroptosis-associated astrocytic activations in the anterior hypothalamus using VX-765 may ameliorate circadian rhythm disorder after trauma. In conclusion, we suggest that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI.

Application of three-dimensional material CZIF-8/CS-MS as adsorbents for the determination of plant growth regulators in Schisandra chinensis.

In this study, we employed a melamine sponge (MS) as the skeleton material and utilized carbonized ZIF-8 (CZIF-8) and chitosan (CS) as the raw materials to prepare CZIF-8/CS-MS, a novel material featuring a three-dimensional interconnected porous network. The resulting CZIF-8/CS-MS material possesses a unique porous structure, significant specific surface area and abundant active sites. These characteristics make CZIF-8/CS-MS a promising absorbent for selective purification of plant growth regulators (PGRs) including 1-naphthlcetic acid (NAA), naphthoxyacetic acid (NOA), 4-chlorophenoxyacetic acid (4-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D). After optimizing the extraction conditions, excellent linearity (r > 0.9994) was observed within a wide linear range of 1-100 ng/mL using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry. The detection limits (LODs) and limits of quantification (LOQs) were found to be in the range of 0.013-0.154 ng/mL and 0.044-0.515 ng/mL, respectively. Additionally, the relative recovery of Schisandra chinensis fruit samples was determined to be 89.7-99.4 %, with a relative standard deviation (RSDs) of ≤ 8.4 % (n = 3). Compared to other methods, this approach offers a multitude of benefits, which include but are not limited to exceptional sensitivity, reduced sample volume requirements, low LODs, a comparable linear range, and high reproducibility. The findings of this study pave the way for exploring novel functionalized sponge columns, which leverage the integration of nano-sorbent materials and coating agents, for the purpose of analyzing PGRs within intricate matrix samples.

NLRP3-GABA signaling pathway contributes to the pathogenesis of impulsive-like behaviors and cognitive deficits in aged mice.

BACKGROUND: Perioperative neurocognitive disorders (PND), such as delirium and cognitive impairment, are commonly encountered complications in aged patients. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is aberrantly synthesized from reactive astrocytes following inflammatory stimulation and is implicated in the pathophysiology of neurodegenerative diseases. Additionally, the activation of NOD-like receptor protein 3 (NLRP3) inflammasome is involved in PND. Herein, we aimed to investigate whether the NLRP3-GABA signaling pathway contributes to the pathogenesis of aging mice's PND. METHODS: 24-month-old C57BL/6 and astrocyte-specific NLRP3 knockout male mice were used to establish a PND model via tibial fracture surgery. The monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) was intraperitoneally administered once a day for 7 days after the surgery. PND, including impulsive-like behaviors and cognitive impairment, was evaluated by open field test, elevated plus maze, and fear conditioning. Thereafter, pathological changes of neurodegeneration were explored by western blot and immunofluorescence assays. RESULTS: Selegiline administration significantly ameliorated TF-induced impulsive-like behaviors and reduced excessive GABA production in reactive hippocampal astrocytes. Moreover, astrocyte-specific NLRP3 knockout mice reversed TF-induced impulsive-like and cognitive impairment behaviors, decreased GABA levels in reactive astrocytes, ameliorated NLRP3-associated inflammatory responses during the early stage, and restored neuronal degeneration in the hippocampus. CONCLUSIONS: Our findings suggest that anesthesia and surgical procedures trigger neuroinflammation and cognitive deficits, which may be due to NLRP3-GABA activation in the hippocampus of aged mice.

CORM-3 alleviates the intestinal injury in a rodent model of hemorrhage shock and resuscitation: roles of GFAP-positive glia.

Hemorrhagic shock and resuscitation (HSR) can induce severe intestinal damages, thereby leading to sepsis and long-term complications including dysbacteriosis and pulmonary injury. The NOD-like receptor protein 3 (NLRP3) inflammasome facilitates inflammation-associated cell recruitment in the gastrointestinal tract, and participates in many inflammatory bowel diseases. Previous studies have shown that exogenous carbon monoxide (CO) exerts neuroprotective effects against pyroptosis after HSR. We aimed to investigate whether carbon monoxide-releasing molecules-3 (CORM-3), an exogenous CO compound, could attenuate HSR-induced intestinal injury and the potential underlying mechanism.Rats were subjected to a HSR model by bleeding and re-infusion. Following resuscitation, 4 mg/kg of CORM-3 was administered intravenously into femoral vein. At 24 h and 7 d after HSR modeling, the pathological changes in intestinal tissues were evaluated by H&E staining. The intestinal pyroptosis, glial fibrillary acidic protein (GFAP)-positive glial pyroptosis, DAO (diamine oxidase) content, intestine tight junction proteins including zonula occludens-1 (ZO-1) and claudin-1 were further detected by immunofluorescence, western blot and chemical assays at 7 d after HSR. CORM-3 administration led to significantly mitigated HSR-induced intestinal injury, aggravation of intestinal pyroptosis indicated by cleaved caspase-1, IL-1ß and IL-18, upregulation of GFAP-positive glial pyroptosis, decreased intensity of ZO-1 and claudin-1 in the jejunum, and increased of DAO in the serum. Nigericin, an agonist of NLRP3, significantly reversed the protective effects of CORM-3. CORM-3 alleviates the intestinal barrier dysfunction in a rodent model of HSR, and the potential mechanism may be associated with inhibition of NLRP3-associated pyroptosis. CORM-3 administration could be a promising therapeutic strategy for intestinal injury after hemorrhagic shock.

Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. METHODS: Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3-dimensional arterial spin labeling (3D-ASL). Apoptosis and pyroptosis were evaluated directly from tissue. RESULTS: In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24 hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6 hours were lower than in the Sham group. MD and Da at 24 hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D-ASL. CONCLUSIONS: Advanced MRI metrics from DKI and 3D-ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia-reperfusion in rats induced by HSR.

Recent advances in emerging application of functional materials in sample pretreatment methods for liquid chromatography-mass spectrometry analysis of plant growth regulators: A mini-review.

Plant growth regulators (PGRs) are a class of small molecular compounds, which can remarkably affect the physiological process of plants. The complex plant matrix along with a wide polarity range and unstable chemical properties of PGRs hinder their trace analysis. In order to obtain a reliable and accurate result, a sample pretreatment process must be carried out, including eliminating the interference of the matrix effect and pre-concentrating the analytes. In recent years, the research of functional materials in sample pretreatment has experienced rapid growth. This review comprehensively overviews recent development in functional materials covering one-dimensional materials, two-dimensional materials, and three-dimensional materials applied in the pretreatment of PGRs before liquid chromatography-mass spectrometry (LC-MS) analysis. Besides, the advantages and limitations of the above functionalized enrichment materials are discussed, and their future trends have been prospected. The work could be helpful to bring new insights for researchers engaged in functional materials in sample pretreatment of PGRs based on LC-MS.

Spautin-1 Protects Against Mild TBI-Induced Anxiety-Like Behavior in Mice via Immunologically Silent Apoptosis.

Anxiety is reportedly one of the most common mental changes after traumatic brain injury (TBI). Perineuronal nets (PNNs) produced by astrocytes in the lateral hypothalamus (LHA) that surround gamma-aminobutyric acid-ergic (GABAergic) neurons have been associated with anxiety. The potent anti-tumor effects of Spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma; moreover, the inhibition of autophagy is reported to mitigate anxiety disorders. However, little is known about the ability of spautin-1 to alleviate anxiety. In this study, we sought to investigate whether spautin-1 could alleviate anxiety-like behaviors post-TBI by reducing the loss of PNNs in the LHA. A mild TBI was established in mice through Feeney's weight-drop model. Then, Spautin-1 (20 mmol/2 µl) was immediately administered into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 days, 30 days, 31 days and 32 days after TBI by the neurological severity scores (NSS), open field test (OFT), elevated plus-maze (EPM) test, western blot, immunofluorescence assays and electron microscopy. Spautin-1 significantly reversed TBI-induced decreased time in the central zone during OFT and in the open-arm during the EPM test. Spautin-1 also increased PNNs around GABAergic neurons indicated by WFA- plus GAD2- positive A2-type astrocytes and attenuated M1-type microglia in the LHA 32 days after TBI compared to TBI alone. Moreover, compared to mice that only underwent TBI, spautin-1 downregulated autophagic vacuoles, abnormal organelles, the expression of Beclin 1, USP13, phospho-TBK1, and phospho-IRF3 and upregulated the levels of cleaved caspase-3, -7 and -9, but failed to increase TUNEL-positive cells in the LHA at 24 h. Spautin-1 alleviated anxiety-like behavior in mice exposed to mild TBI; this protective mechanism may be associated with decreased PNNs loss around GABAergic neurons via immunologically silent apoptosis induced by the caspase cascade.

Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice via activation of caspase-3.

BACKGROUND: Cognitive and memory dysfunction, a common sequela of traumatic brain injury (TBI), places a heavy social and economic burden on individuals, families, communities, and countries. Although the potent anti-tumor effects of spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma, little is known regarding its efficacy on alleviation of cognitive and memory dysfunction. Here, we describe the effect of spautin-1 administration on cognitive and memory impairment post-TBI, and reveal its underlying mechanism of action. METHODS: We first induced mild TBI in mice through Feeney's weight-drop model, then immediately administered spautin-1 (10 mmol/µl, 2 µl) into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 and 30 days after TBI by analyzing neurological severity scores (NSS), novel objective recognition (NOR), Morris water maze (MWM) test, recording of local field potential (LFP), as well as western blot, and immunofluorescence assays. RESULTS: Mild TBI not only reduced recognition index and times crossing platform, but also aggravated neuronal injury, including reduced MAP2, GAD2, VGlut2, and CHAT intensity. It also elevated activated microglia and CD86-occupied areas in TMEM119-positive cells, but suppressed θ, ß, and γ oscillation power in the hippocampal CA1. However, spautin-1 administration significantly reversed these changes, whereas AC-DEVD-CHO an inhibitor of caspase-3 partially blocked the neuroprotective effects of spautin-1. CONCLUSION: Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice, potentially through activation of caspase-3.

Abdominal surgery plus sevoflurane exposure induces abnormal emotional changes and cognitive dysfunction in aged rats.

BACKGROUND: Cognitive impairment, which includes perioperative psychological distress and cognitive dysfunction, can be determined by preoperative and post-operative neuropsychological tests. Several mechanisms have been proposed regarding the two-way communication between the immune system and the brain after surgery. We aimed to understand the mechanisms underlying perioperative neurocognitive disorders (PND) in elderly rats using an experimental abdominal surgery model. METHODS: 24-month-old SD rats were exposed to the abdominal surgery model (AEL) under 3% anesthesia. On day 15 and day 30 post-surgery, fractional anisotropy (FA) using diffusion kurtosis imaging (DKI) was measured. From day 25 to day 30 post-surgery, behavioral tests, including open field test (OFT), Morris water maze (MWM), novel object recognition (NOR), force swimming test (FST), and elevated plus maze (EPM), were performed. Then, the rats were euthanized to perform pathological analysis and western blot measurement. RESULTS: The rats exposed to AEL surgical treatment demonstrated significantly decreased time crossing the platform in the MWM, decreased recognition index in the NOR, reduced time in the open arm in the EPM, increased immobility time in the FST, and increased number of crossings in the OFT. Aged rats, after AEL exposure, further demonstrated decreased FA in the mPFC, nucleus accumbens (NAc), and hippocampus, together with reduced MAP2 intensity, attenuation of GAD65, VGlut2, CHAT, and phosphorylated P38MAPK expression, and increased reactive astrocytes and microglia. CONCLUSIONS: In this study, the aged rats exposed to abdominal surgery demonstrated both emotional changes and cognitive dysfunction, which may be associated with neuronal degeneration and reduced phosphorylated P38MAPK.

[Systemic Influencing Factors of Dentition Defect in Type 2 Diabetes Mellitus Patients with Periodontitis].

Objective: To analyze the influencing factors of dentition defect in people with type 2 diabetes mellitus (T2DM) and periodontitis and to provide evidence-based support for improving the oral health and quality of life of T2DM patients. Methods: A total of 169 patients with T2DM and periodontitis were selected by convenience sampling. According to the number of remaining teeth, the subjects were divided into two groups, group A (number of remaining teeth in the mouth≥20, n=115) and group B (the number of remaining teeth in the mouth<20, n=54). Questionnaire surveys, systemic and oral examinations, and laboratory blood tests were performed. Systematic influencing factors of dentition defect in people with T2DM and periodontitis were analyzed with logistic regression. Results: Compared with patients in group A, patients in group B had higher findings in age, systolic blood pressure (SBP), prevalence of coronary heart disease and hyperlipidemia, glycosylated hemoglobin (HbA1c), periodontal probing depth (PD), and clinical attachment loss (CAL). Furthermore, their behaviors and awareness of oral health were not as good as those of patients in group A. Logistic regression showed that age, HbA1c, and SBP were independent risk factors for the number of remaining teeth in the mouth <20 among T2DM patients with periodontitis ( P<0.05). Conclusion: Increasing age, lower HbA1c, and increased SBP are the most important influencing factors for the number of remaining teeth in the mouth <20 in T2DM patients with periodontitis. Clinical practitioners should give more attention to the general health status of the patients and strengthen health education, thereby improving patients' quality.

IL-18BP Alleviates Anxiety-Like Behavior Induced by Traumatic Stress via Inhibition of the IL-18R-NLRP3 Signaling Pathway in a Mouse Model of Hemorrhagic Shock and Resuscitation.

Psychological distress and posttraumatic stress, including anxiety, severely influence life quality. Previously, we reported that interleukin-18 (IL-18) was involved in pyroptosis-induced emotional changes in a rodent model of hemorrhagic shock and resuscitation (HSR). Here, we aimed to continue our investigation on the role of IL-18 binding protein (IL-18BP), which exhibits excellent anti-inflammatory effects as an IL-18 negative regulator. Mice were administered with an intraperitoneal injection of IL-18BP after HSR exposure and anxiety-like behavior was examined using the open-field test and elevated plus maze test. Moreover, the following variables post-HSR were measured: (1) the activation of astrocytes; (2) pyroptosis-associated factors including cleaved caspase-1, GSDMD, IL-18; (3) the roles of IL-18 receptor (IL-18R)-NOD-like receptor pyrin domain-containing-3 (NLRP3) signal with the application of the NLRP3 specific agonist or astrocyte-specific NLRP3 knockout mice. IL-18BP administration remarkably alleviated HSR-induced anxiety-like behavior, astrocytic activation, and increases in pyroptosis-associated factors, while NLRP3 agonist nigericin partially reversed IL-18BP-induced neuroprotective effects. Astrocyte-specific NLRP3 knockout mice exhibited relatively less anxiety-like behavior. Similarly, IL-18BP exhibited an anti-pyroptosis effect in astrocytes in an in vitro model of low oxygen-glucose deprivation. These findings offer unique perspectives on HSR-induced posttraumatic stress and indicate that inhibition of IL-18R-NLRP3 signal via IL-18BP can attenuate astrocytic activation and pyroptosis, broadening the therapeutic landscape for patients with psychological distress and posttraumatic stress.

Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress.

Post-stroke chronic stress (PSCS) is generally associated with the poorer recovery and more pronounced cognitive dysfunction. Recent evidence has implied that S-ketamine can reduce suicidal ideation in treatment-resistant depression. In this current study, we aimed to investigate whether the administration of S-ketamine ameliorated cognitive deficits under PSCS conditions, which was established by a model combining middle cerebral artery occlusion (MCAO) and chronic restraint stress. Our data suggested that mice exposed to PSCS exhibited depression-like behavior and cognitive impairment, which coincided with astrocytosis as indicated by increased GFAP-positive cells and impairment of long-time potentiation (LTP) in the hippocampal CA1. Subanesthetic doses (10 mg/kg) of S-ketamine have significantly mitigated depression-like behaviors, cognitive deficits and LTP impairment, reduced astrocytosis, excessive GABA, and inflammatory factors, including NLRP3 and IL-18 in astrocytes in the CA1. Besides, neuroprotective effects induced by S-ketamine administration were found in vitro but could be partially reversed by an agonist of the NLRP3 nigericin. Our current data also suggests that the subanesthetic doses of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of PSCS.

S-ketamine administration in pregnant mice induces ADHD- and depression-like behaviors in offspring mice.

BACKGROUND: Anesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice. METHODS: Pregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14-18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay. RESULTS: All the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus. CONCLUSIONS: These results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.

STING mediates neuroinflammatory response by activating NLRP3-related pyroptosis in severe traumatic brain injury.

Long-term neurological deficits after severe traumatic brain injury (TBI), including cognitive dysfunction and emotional impairments, can significantly impair rehabilitation. Glial activation induced by inflammatory response is involved in the neurological deficits post-TBI. This study aimed to investigate the role of the stimulator of interferon genes (STING)-nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) signaling in a rodent model of severe TBI. Severe TBI models were established using weight-drop plus blood loss reinfusion model. Selective STING agonist ADU-S100 or antagonist C-176 was given as a single dose after modeling. Further, NLRP3 inhibitor MCC950 or activator nigericin, or caspase-1 inhibitor VX765, was given as an intracerebroventricular injection 30 min before modeling. After that, a novel object recognition test, open field test, force swimming test, western blot, and immunofluorescence assays were used to assess behavioral and pathological changes in severe TBI. Administration of C-176 alleviated TBI-induced cognitive dysfunction and emotional impairments, neuronal loss, and inflammatory activation of glia cells. However, the administration of STING agonist ADU-S100 exacerbated TBI-induced behavioral and pathological changes. In addition, STING activation exacerbated pyroptosis-associated neuroinflammation via promoting glial activation, as evidenced by increased cleaved caspase-1 and GSDMD N-terminal expression. In contrast, the administration of C-176 showed anti-pyroptotic effects. The neuroprotective effects of C-176 were partially reversed by the NLRP3 activator, nigericin. Collectively, glial STING is responsible for neuroinflammation post-TBI. However, pharmacologic inhibition of STING led to a remarkable improvement of neuroinflammation partly through suppressing NLRP3 signaling. The STING-NLRP3 signaling is a potential therapeutic target in TBI-induced neurological dysfunction.

Men's Sleep Quality and Assisted Reproductive Technology Outcomes in Couples Referred to a Fertility Clinic: A Chinese Cohort Study.

Background: Poor sleep quality has been linked to lower semen quality, but it is unclear whether this result in decreased fertility. To address this question, we retrospectively evaluated the relationship between men's sleep quality and treatment outcomes in subfertile couples receiving assisted reproductive technology (ART). Patient Enrollment and Methods: From September 2017 to November 2019, 282 subfertile couples referred to a Chinese fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, life habits, and sleep habits in the year prior to ART were recorded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). We first divided the patients into two groups based on sleep quality (good sleep: PSQI < 5 and poor sleep: PSQI ≥ 5). Then, the ART outcomes (fertilization rate, good quality embryo rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, live birth rate, miscarriage rate, and birth weight) of each group were analyzed. Finally, multivariate linear and logistic regression analysis were used to examine the relationship between sleep quality (discrete variable or dichotomous variable) and ART outcomes. Results: The participants in the poor sleep group showed a lower fertilization rate of 60.13% (543/903) when compared with 67.36% for the good sleep group (902/1339), P < 0.001. The global PSQI score had a significant influence on birth weight (ß, -63.81; 95% CI, -119.91- -8.52; P = 0.047), and live birth rate (OR, 0.88; 95% CI, 0.78- 0.99; P = 0.047) after adjusting for the interfering factors. Men's sleep quality was unrelated to good quality embryos rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, or miscarriage rate. Conclusion: Men's sleep quality was positively associated with fertilization rate, birth weight, and live birth rate among couples undergoing ART.

CORM-3 exerts a neuroprotective effect in a rodent model of traumatic brain injury via the bidirectional gut-brain interactions.

OBJECTIVE: Traumatic brain injury (TBI) induced the gastrointestinal inflammation that is associated with TBI-related morbidity and mortality. Carbon monoxide-releasing molecule (CORM)-3 is a water-soluble exogenous carbon monoxide that exerts protective effects against inflammation-induced pyroptosis. We investigated the gastrointestinal inflammation in a rodent model of traumatic brain injury (TBI) with subsequent hemorrhagic shock and resuscitation (HSR), as well as effects of CORM-3 using an intestinal injection on both gut and brain. METHODS: Following exposure to TBI plus HSR, rats were administrated with CORM-3 (8 mg/kg) through an intestinal injection after resuscitation immediately. The pathological changes and pyroptosis in the gut were measured at 24 h and 30 day post-trauma. We also assessed the intestinal and cortical CO content, as well as IL-1ß and IL-18 levels in the serum within 48 h after trauma. We then explored pathological changes in the ventromedial prefrontal cortex (vmPFC) and neurological behavior deficits on 30 day post-trauma. RESULTS: After TBI + HSR exposure, CORM-3-treated rats presented significantly decreased pyroptosis, more CO content in the jejunum, and lower IL-1ß, IL-18 levels in the serum at 24 h after trauma. Moreover, the rats treated with CORM-3 exerted ameliorated jejunal and vmPFC injury, enhanced learning/memory ability and exploratory activity, improved anxiety-like behaviors than the TBI + HSR-treated rats on 30 day post-trauma. CONCLUSION: These experimental data demonstrated and bidirectional gut-brain interactions after TBI, anti-inflammatory effects of CORM-3, which may improve late outcomes after brain injury.

Decreased LF/HF ratio is associated with worse outcomes in patients who received mechanical thrombectomy under general anesthesia for emergent large vessel occlusion: a retrospective study.

BACKGROUND AND PURPOSE: We aimed to determine whether heart rate variability (HRV) was correlated to long-term outcome in patients who received mechanical thrombectomy (MT) under general anesthesia for emergent large vessel occlusion (ELVO). METHODS: Data from 106 patients receiving MT under general anesthesia to treat ELVO between January 1, 2017 and December 31, 2019 were collected in a multicenter chart review. Univariate analysis, Chi-square test, and bivariate logistic regression were performed to assess the correlations between preoperative risk factors such as HRV and long-term outcome (as indicated by the modified Rankin score [mRS] at 90 days after MT). RESULTS: Bivariate logistic regression revealed that decreased LF/HF (low frequency/high frequency in HRV) ratio was correlated with unfavorable functional outcome as indicated by mRS ≥ 2 (odds ratio [OR], 0.650; 95% confidence interval [CI], 0.157-0.839; p = 0.018), and functionally dependent outcome as indicated by mRS ≥ 3 (OR, 0.704; 95% CI, 0.360-0.914; p = 0.021). It was also found that ELVO in the right anterior circulation was correlated with lower LF/HF ratio, as compared with ELVO in the contralateral side (p < 0.05). CONCLUSION: Our retrospective study demonstrated that worse outcome in patients with ELVO who received MT under general anesthesia induced autonomic changes and that decreased LF/HF ratio.

Decrease of Coronal Optic Nerve Sheath Diameter is Associated With Postoperative Cognitive Decline in Patients Undergoing Carotid Endarterectomy.

OBJECTIVE: Patients undergoing carotid endarterectomy (CEA) have a significant possibility of developing postoperative cognitive decline (POCD). POCD after surgery could be result from cerebral hypotension induced by cross-clamping or postoperative hyperperfusion. Optic nerve sheath diameter (ONSD) exhibits an excellent correlation with invasive intracranial pressure monitoring, Here, the authors explored the risk factors of POCD in patients undergoing CEA, paying close attention to ONSD to test the hypothesis that decrease of coronal ONSD was related to the incidence of POCD. DESIGN: Observational retrospective review. SETTING: Single tertiary academic center. PARTICIPANTS: One hundred sixteen patients undergoing CEA from January 1, 2019 to December 31, 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A multivariate logistic regression, scatter diagrams, and a receiver operating curve were used to evaluate the ability to predict POCD though the change in coronal ONSD. This study ultimately enrolled 84 patients and the incidence of POCD within postoperative two days was 28.6%. Decrease of coronal ONSD (odds ratio [OR], 0.438; 95% confidence interval [CI] 0.217-0.881; p = 0.021) and total intravenous anesthesia (TIVA) (OR, 25.541, 95% CI 2.100-310.614, p = 0.011) were independent risk factors for POCD. Changes in coronal ONSD had an area under the curve to distinguish POCD of 0.716 (95% CI 0.531-0.902). Using a cutoff of 0.05 cm, changes of coronal ONSD had a sensitivity of 66.7% and specificity of 66.7%. CONCLUSIONS: Decrease of coronal ONSD, measured by ultrasonography and TIVA, were associated with POCD. Change in coronal ONSD was a moderate predictor of incidence of POCD.