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Quan-fang Liu,1 Cui-na Shi,1 Jian-hua Tong,1 Kun-peng Li,1 Jian-jun Yang,2 Mu-huo Ji,1 Qing-ren Liu3 1Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of ChinaCorrespondence: Qing-ren Liu, Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China, Email liuqr5250@163.com Mu-huo Ji, Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China, Email jimuhuo2009@sina.comBackground: The utilization of adjuvants such as dexamethasone and dexmedetomidine in combination with local anesthetics has proven effective in extending analgesia duration. We aimed to investigate the potential efficacy of combining dexmedetomidine and dexamethasone in rhomboid intercostal and sub-serratus (RISS) block for prolonging postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS).Methods: We did this randomized, double-blind, controlled trial in two tertiary-care hospitals. A total of eighty-eight patients undergoing VATS under general anesthesia were enrolled in this study. They were randomly assigned into four groups: ropivacaine (R) group, ropivacaine + dexmedetomidine (RM) group, ropivacaine + dexamethasone (RS) group, or ropivacaine + dexmedetomidine + dexamethasone (RSM) group. The primary outcome measure was the duration of analgesia. Secondary outcomes included Numeric Rating Scale (NRS) scores, cumulative oxycodone consumption, and adverse effects.Results: The RSM group exhibited a significantly prolonged duration of analgesia at 1073.5 min (932.0– 1283.3) compared to the R group with a duration of 154.5 min (80.5– 199.3) and the RS group with a duration of 282.0 min (195.3– 350.0, P < 0 0.001). The cumulative oxycodone consumption during the 0– 12 hours and 0– 24-hours period was significantly reduced in the RSM group compared to the R group (P < 0.05). There was also a lower incidence of nausea at 48 hours postoperatively in the RSM group compared to the RM group. However, there were no significant differences between the four groups regarding NRS pain scores.Conclusion: The combination of ropivacaine, dexmedetomidine, and dexamethasone in RISS block significantly prolongs the duration of postoperative analgesia following VATS.Keywords: nerve block, pain, postoperative, anesthesia, video-assisted thoracoscopic surgery

Qing-Ren Liu,1 Yu-Chen Dai,2 Mu-Huo Ji,3 Pan-Miao Liu,4 Yong-Yan Dong,4 Jian-Jun Yang4 1Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 2Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 4Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, People’s Republic of ChinaCorrespondence: Jian-Jun Yang, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, NO. 1 East Jianshe Road, Zhengzhou, 450052, People’s Republic of China, Email yjyangjj@126.comAbstract: Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.Keywords: acute postoperative pain, acute postsurgical pain, risk factors, predictors

Marco H Ji,1 Natalia F Callaway,1 Margaret A Greven,2 Daniel Vail,1 Darius M Moshfeghi1 1Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California; 2Department of Ophthalmology, Wake Forest University School of Medicine, Winston-Salem, North CarolinaCorrespondence: Darius M Moshfeghi Tel +1 (650) 723-6995Email dariusm@stanford.eduAbstract: Telemedicine has emerged as a potential solution to face the disproportion between infants that need to be screened for retinopathy of prematurity (ROP) and the lack of ophthalmologists. We evaluated its utility in the follow-up after off-label intravitreal injection of bevacizumab. None of the treated infants ended up with bad anatomic outcome. Telemedicine is an alternative safe method to monitor patients after treatment.Keywords: pediatric retina, retina, pediatric ophthalmology

Sleep is pivotal to memory consolidation, and sleep deprivation (SD) after learning can impede this process, leading to memory disorders. In the present study, we aimed to explore the effects of acute sleep deprivation (ASD) on memory disorders and the underlying mechanisms. ASD model was induced by subjecting the mice to 6 h of SD following fear conditioning training. Different cohorts were used for behavioral, biochemical, and electrophysiological tests. Here, we showed that memory precision decline was induced by ASD, concomitant with a notable elevation in oxidative stress within PV interneurons, loss of PV, and disturbed neuronal oscillation in the CA1 region. Notably, chemogenetic activation of PV interneurons effectively ameliorated abnormal gamma oscillation and memory precision decline observed in ASD mice. Meanwhile, chemogenetic inhibition of PV interneurons successfully mimicked the abnormal brain oscillations and memory precision decline observed in ASD mice. Additionally, prior administration of the antioxidant medication N-acetylcysteine effectively reversed memory precision decline and mitigated PV loss and abnormal oscillation triggered by ASD. Collectively, our findings indicated that ASD increased oxidative stress in PV interneurons, thereby disrupting neural oscillation in the CA1 and ultimately leading to memory precision decline., Competing Interests: Declarations Ethics Approval All the animal experiments were approved by the Ethics Committee of Nanjing Medical University, and all procedures were performed in accordance with the approved guidelines. Consent to Participate Not applicable. Consent for Publication Not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To quantify chorioretinal microvascular damage and recovery post-treatment in patients with acute syphilitic posterior placoid chorioretinitis (ASPPC) using fractal dimension (FD)., Methods: Retrospective cohort study of patients with serologically confirmed syphilitic uveitis. We obtained optical coherence tomography angiography (OCTA) scans at baseline and follow-up after intravenous penicillin treatment and computed FD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using ImageJ., Results: We enrolled seven patients with ASPPC (11 eyes), and 17 control subjects (34 eyes). Pre-treatment averages of FD-SCP, FD-DCP, and FD-CC were: 1.672 (±0.115), 1.638 (±0.097), and 1.72 (±0.137); post-treatment: 1.760 (±0.071), 1.764 (±0.043), and 1.898 (±0.047). After treatment FD-CC increased in all 11 eyes with an average of 0.163 ( p  = 0.003); FD-DCP increased in 10 (91%) eyes with an average of 0.126 ( p  = 0.003); and FD-SCP increased in seven (64%) eyes with an average of 0.089 ( p  = 0.059). Compared to the post-treatment FD values in the syphilitic group, controls had similar FD-SCP ( p  = 0.266), FD-DCP ( p  = 0.078), and FD-CC ( p  = 0.449)., Conclusions: CC and DCP are mostly affected in ASPPC with minimal changes in the SCP. All vascular layers FD recovered after completing antibiotic treatment.

Purpose: This study compared two imaging grading techniques to assess the utility of longitudinal image-based analysis in retinopathy of prematurity (ROP) screening: (1) time-limited without image comparison (a proxy for bedside indirect ophthalmoscopy, termed sBIO) and time-unlimited with image comparison (for telemedicine grading, termed TELE) screening. We tested two hypotheses: (1) H1: TELE was superior to sBIO for the detection of change (Tempo)-same, better, or worse and (2) H2: granular data of change (e.g., at the image and feature level) is integrated by graders to achieve the Tempo assessment., Design: Prospective reliability analysis., Methods: Gold standard reference (GS) was a published curated ROP image database consisting of both Tempo and granular level changes (image and components) from 40 patients in 2 sets. Graders were divided into 2 cohorts. There were two screening techniques: (1) sBIO with time limited review of 10 minutes/patient, access to prior notes and drawings and (2) TELE with unlimited review time, access to prior weeks' images, notes and schematics. Graders switched techniques and sets after 6 weeks. H1 outcome was comparison of graders' weekly Tempo scores to GS-Gestalt and for H2 was Tempo score compared to GS-View and GS-Component., Results: H1 demonstrated no difference-accuracy of sBIO and TELE compared to GS was 51.7% and 51.9% respectively (P = .95). Highest agreement occurred when all exams exhibited no change (91.5% sBIO vs 93.5% TELE, P = .46) and worst agreement was when exams always demonstrated worsening (46.5% sBIO vs 47.1% TELE, P = .93). Both sets of graders did worse in weeks 7-12, irrespective of technique. H2 demonstrated that Tempo assessment did not correlate with granular data changes in the GS for View level and Component level assessments-overall agreement dropped to 31.4% for Tempo vs GS-VIEW (31.2% for sBIO, 31.5% for TELE) and 4.6% for Tempo vs GS-COMPONENT (4.9% for sBIO, 4.3% for TELE)., Conclusions: Detection of ROP Tempo was independent of screening technique by expert pediatric retina graders. Both groups did significantly better in the first half of the study, indicative of a fatigue factor. This is the first study in ROP history to demonstrate that graders integrate image and retinal features in various ways that can be in contradiction of their assessment of overall disease progression., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Postoperative neurocognitive disorders (pNCD) are a common neurological complication, especially in elderly following anesthesia and surgery. Yet, the underlying mechanisms of pNCD remain elusive. This study aimed to investigate the molecular mechanisms that compromise synaptic metaplasticity in pNCD development with a focus on the involvement of Nogo-66 receptor 1 (NgR1) in the pathogenesis of pNCD in aged mice. Aged mice subjected to anesthesia and laparotomy surgery exhibited anxiety-like behavior and contextual fear memory impairment. Moreover, the procedure significantly increased NogoA and NgR1 expressions, particularly in the hippocampal CA1 and CA3 regions. This increase led to the depolymerization of F-actin, attributed to the activation of the RhoA-GTPase, resulting in a reduction of dendritic spines and changes in their morphology. Additionally, these changes hindered the efficient postsynaptic delivery of the subunit GluA1 and GluA2 of AMPA receptors (AMPARs), consequently diminishing excitatory neurotransmission in the hippocampus. Importantly, administering the competitive NgR1 antagonist peptide NEP1-40 (Nogo-A extracellular peptide residues 1-40 amino acids of Nogo-66) and Fasudil (a Rho-kinase inhibitor) effectively mitigated synaptic impairments and reversed neurocognitive deficits in aged mice following anesthesia and surgery. Our work indicates that high hippocampal Nogo66-NgR1 signaling disrupts postsynaptic AMPA receptor surface delivery due to F-actin depolymerization in the pathophysiology of pNCD., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Accumulative evidence suggested that the oxytocin system plays a role in socio-emotional disorders, although its role in neuroinflammation-induced anxiety remains unclear., Method: In the present study, anxiety-like behavior was induced in cohorts of animals through repeated lipopolysaccharide (LPS, 0.5 mg/kg, daily, Escherichia coli O55:B5) i.p. injections for seven consecutive days. These different cohorts were subsequently used for anxiety-like behavior assessment with open field test, elevated plus maze, and novelty-suppressed feeding test or for electrophysiology (EEG) recordings of miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs), or local field potential (LFP) in vivo or ex vivo settings. Samples of the anterior cingulate cortex (ACC) from some cohorts were harvested to conduct immunostaining or western blotting analysis of oxytocin, oxytocin receptor, CamkII, GABA, vGAT, vGLUT2, and c-fos. The dendritic spine density was assessed by Golgi-Cox staining., Results: Repeated LPS injections induced anxiety-like behavior with concurrent decreases of oxytocin, vGLUT2, mEPSC, dendritic spine, c-fos, membrane excitability, and EEG beta and gamma oscillations, but increased oxytocin receptor and vGAT expressions in the ACC; all these changes were ameliorated by oxytocin intranasal or local brain (via cannula) administration., Conclusion: Taken together, our data suggested that oxytocin system may be a therapeutic target for developing treatment to tackle neuroinflammation-induced anxiety., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neuroinflammation, characterized by activation of glial cells, plays a critical role in central nervous system disorders. However, the precise mechanisms of neuroinflammation contributing to cognitive impairment remain elusive. Perineuronal nets (PNNs) are extracellular matrixes that envelop the cell bodies and dendrites of parvalbumin (PV)-positive interneurons and may be mediated by apolipoprotein E (ApoE) gene. To investigate whether disruption of PNNs associated with ApoE is implicated in neuroinflammation-induced cognitive impairment, we established a neuroinflammation model by administering lipopolysaccharides (LPS) at 0.5 mg/kg for 7 consecutive days. Cognitive function was assessed using the open field, Y-maze, and novel object recognition tests, and neural oscillations were also recorded. Furthermore, differentially expressed genes in microglia within the hippocampus were identified through single-cell RNA sequencing analysis. Overexpression of hyaluronan and proteoglycan link protein 1 (Hapln1) and ApoE knockdown were carried out through adeno-associated virus (AAV) injection to C57BL/6J mice and CX3CR1-CreERT2 mice, respectively. It was found that LPS-induced neuroinflammation impaired cognitive function by reducing PNNs and PV-positive interneurons' outputs, as well as disrupting gamma (γ) oscillations in the hippocampal CA1. Overexpression of Hapln1 was able to restore PV-positive interneurons and γ oscillations, ultimately alleviating the cognitive impairment. Mechanistically, LPS-triggered microglial activation leads to the phagocytosis of PNNs, a process influenced by ApoE. Notably, prevention of PNNs engulfment through targeting microglial ApoE in the CA1 improved cognitive impairment. Collectively, our study suggested that microglial phagocytosis of PNNs plays a key role in neuroinflammation-induced cognitive impairment, which is probably mediated by the ApoE., Competing Interests: Declaration of competing interest All the other authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations., Patients and Methods: This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone., Results: Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR ( P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047)., Conclusion: Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:511-516.] .

Purpose: Central retinal artery occlusion (CRAO) is an ocular emergency that results from acute blockage of the blood supply to the retina and leads to a sudden vision loss. Other forms of ischemic retinopathies include diabetic retinopathy (DR), which involves chronic retinal ischemia and remains the leading cause of blindness in working-age adults. This study is the first to conduct a proteomic analysis of aqueous humor (AH) from patients with CRAO with a comparative analysis using vitreous humor (VH) samples from patients with DR., Methods: AH samples were collected from 10 patients with CRAO undergoing paracentesis and 10 controls undergoing cataract surgery. VH samples were collected from 10 patients with DR and 10 non-diabetic controls undergoing pars plana vitrectomy (PPV). Samples were analyzed using mass spectrometry., Results: Compared with controls, AH levels of 36 differentially expressed proteins (DEPs) were identified in patients with CRAO. Qiagen Ingenuity Pathway Analysis (IPA) revealed 11 proteins linked to ophthalmic diseases. Notably, enolase 2, a glycolysis enzyme isoform primarily expressed in neurons, was upregulated, suggesting neuronal injury and enzyme release. Additionally, clusterin, a protective glycoprotein, was downregulated. ELISA was conducted to confirm proteomics data. VH samples from patients with DR exhibited changes in a distinct set of proteins, including ones previously reported in the literature., Conclusions: The study provides novel insights into CRAO pathophysiology with multiple hits identified. Proteomic results differed between DR and CRAO studies, likely due to the different pathophysiology and disease duration., Translational Relevance: This is the first proteomic analysis of CRAO AH, with the potential to identify future therapeutic targets.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Purpose: RP2-associated retinopathy typically causes severe early onset retinitis pigmentosa (RP) in affected males. However, there is a scarcity of reports describing the clinical phenotype of female carriers. We tested the hypothesis that RP2 variants manifest in female carriers with a range of functional and anatomic characteristics., Design: Retrospective case series., Methods: Females with disease-causing variants in RP2 were identified from investigation of pedigrees affected by RP2 retinopathy. All case notes and results of molecular genetic testing, retinal imaging (fundus autofluorescence imaging, optical coherence tomography (OCT)), and electrophysiology were reviewed., Results: Forty pedigrees were investigated. Twenty-nine pedigrees had obligate carriers or molecularly confirmed female members with recorded relevant history and/or examination. For 8 pedigrees, data were available only from history, with patients reporting affected female relatives with RP in 4 cases and unaffected female relatives in the other 4 cases. Twenty-seven females from 21 pedigrees were examined by a retinal genetics specialist. Twenty-three patients (85%) reported no complaints and had normal vision and 4 patients had RP-associated complaints (15%). Eight patients had normal fundus examination (30%), 10 had a tapetal-like reflex (TLR; 37%), 5 had scattered peripheral pigmentation (19%), and the 4 symptomatic patients had fundus findings compatible with RP (15%). All asymptomatic patients with normal fundus, TLR, or asymptomatic pigmentary changes had a continuous ellipsoid zone on OCT when available. The electroretinograms revealed mild to severe photoreceptor dysfunction in 9 of 11 subjects, often asymmetrical, including 5 with pattern electroretinogram evidence of symmetrical (n = 4) or unilateral (n = 1 subject) macular dysfunction., Conclusions: Most carriers were asymptomatic, exhibiting subclinical characteristics such as TLR and pigmentary changes. However, female carriers of RP2 variants can manifest RP. Family history of affected females with RP does not exclude X-linked disease. The phenotypic spectrum as described herein has prognostic and counselling implications for RP2 carriers and patients., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the genetic and clinical features and the natural history of RBP3-associated retinopathy., Design: Multi-center international, retrospective, case series of adults and children, with moleculraly confirmed RBP3-asociated retinopathy., Methods: The genetic, clinical, and retinal imaging findings, including optical coherence tomography (OCT) and fundus autofluorescence (FAF), were investigated both cross-sectionally and longitudinally. The results of international standard full-field electroretinography (ERG) and pattern electroretinography (PERG) were reviewed., Results: We ascertained 12 patients (5 female and 7 male) from 10 families (4 patients previously reported). Ten novel disease-causing RBP3 variants were identified. Ten patients were homozygous. The mean age (±SD, range) of the group was 21.4 years (±19.1, 2.9-60.5 years) at baseline evaluation. All 12 patients were highly myopic, with a mean spherical equivalent of -16.0D (range, -7.0D to -33.0D). Visual acuity was not significantly different between eyes, and no significant anisometropia was observed. Mean best-corrected visual acuity (BCVA) was 0.48 logMAR (SD, ±0.29; range, 0.2-1.35 logMAR); at baseline. Eleven patients had longitudinal BCVA assessment, with a mean BCVA of 0.46 logMAR after a mean follow-up of 12.6 years. All patients were symptomatic with reduced VA and myopia by the age of 7 years old. All patients had myopic fundi and features in keeping with high myopia on OCT, including choroidal thinning. The 4 youngest patients had no fundus pigmentary changes, with the rest of the patients presenting with a variable degree of mid-peripheral pigmentation and macular changes. FAF showed variable phenotypes, ranging from areas of increased signal to advanced atrophy in older patients. OCT showed cystoid macular edema at presentation in 3 patients, which persisted during follow-up in 2 patients and resolved to atrophy in the third patient. The ERGs were abnormal in 9 of 9 cases, revealing variable relative involvement of rod and cone photoreceptors with additional milder dysfunction post-phototransduction in some. All but 1 patient had PERG evidence of macular dysfunction, which was severe in most cases., Conclusions: This study details the clinical and functional phenotype of RBP3-retinopathy in the largest cohort reported to date. RBP3-retinopathy is a disease characterized by early onset, slow progression over decades, and high myopia. The phenotypic spectrum and natural history as described herein has prognostic and counseling implications. RBP3-related disease should be considered in children with high myopia and retinal dystrophy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aβ42/Aβ40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aβ42/Aβ40 levels (r = -0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aβ-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance., Competing Interests: Declaration of Competing Interest The authors declare that there are no competing financial interests in relation to the work described., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP's totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed., (© 2023. Springer Nature Limited.)

Repeated neonatal exposures to sevoflurane induce long-term cognitive impairment that has been reported to have sex-dependent differences. Exercise promotes learning and memory by releasing lactate from the muscle. The study tested the hypothesis that lactate may improve long-term cognitive impairment induced by repeated neonatal exposures to sevoflurane through SIRT1-mediated regulation of adult hippocampal neurogenesis and synaptic plasticity. C57BL/6 mice of both genders were exposed to 3% sevoflurane for 2 h daily from postnatal day 6 (P6) to P8. In the intervention experiments, mice received lactate at 1 g/kg intraperitoneally once daily from P21 to P41. Behavioral tests including open field (OF), object location (OL), novel object recognition (NOR), and fear conditioning (FC) tests were performed to assess cognitive function. The number of 5-Bromo-2'- deoxyuridine positive (BrdU + ) cells and BrdU + /DCX + (doublecortin) co-labeled cells, expressions of brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal-associated protein (Arc), early growth response 1 (Egr-1), SIRT1, PGC-1α and FNDC5, and long-term potentiation (LTP) were evaluated in the hippocampus. Repeated exposures to sevoflurane induced deficits in OL, NOR and contextual FC tests in male but not female mice. Similarly, adult hippocampal neurogenesis, synaptic plasticity-related proteins and hippocampal LTP were impaired after repeated exposures to sevoflurane in male but not female mice, which could rescue by lactate treatment. Our study suggests that repeated neonatal exposures to sevoflurane inhibit adult hippocampal neurogenesis and induce defects of synaptic plasticity in male but not female mice, which may contribute to long-term cognitive impairment. Lactate treatment rescues these abnormalities through activation of SIRT1., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Sepsis is a severe host response to infection, which induces both acute and long-term cognitive impairment. Despite its high incidence following sepsis, the underlying mechanisms remain elusive and effective treatments are not available clinically., Area Covered: This review focuses on elucidating the pathological mechanisms underlying cognitive impairment following sepsis. Specifically, the authors discuss the role of systemic inflammation response, blood-brain barrier disruption, neuroinflammation, mitochondrial dysfunction, neuronal dysfunction, and Aβ accumulation and tau phosphorylation in cognitive impairment after sepsis. Additionally, they review current strategies to ameliorate cognitive impairment., Expert Opinion: Potential interventions to reduce cognitive impairment after sepsis include earlier diagnosis and effective infection control, hemodynamic homeostasis, and adequate brain perfusion. Furthermore, interventions to reduce inflammatory response, reactive oxygen species, blood-brain barrier disruption, mitochondrial dysfunction, neuronal injury or death could be beneficial. Implementing strategies to minimize delirium, sleep disturbance, stress factors, and immobility are also recommended. Furthermore, avoiding neurotoxins and implementing early rehabilitation may also be important for preventing cognitive impairment after sepsis.

Background/aims: Flagellin, which is abundant in gram-negative bacteria, including Pseudomonas , is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation., Methods: Normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells., Results: Altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling., Conclusions: These findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling., (© 2023 The Author(s).)

Accumulating evidence has suggested that a great proportion of sepsis survivors suffer from long-term cognitive impairments after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. However, the underlying mechanism remains unclear. In the present study, we established a mouse model of systemic inflammation by repeated lipopolysaccharide (LPS) injections. A combination of behavioral tests, biochemical, and in vivo electrophysiology techniques were conducted to test whether abnormal NRG1/ErbB4 signaling, parvalbumin (PV) interneurons, and hippocampal neural oscillations were involved in memory decline after repeated LPS injections. Here, we showed that LPS induced long-term memory decline, which was accompanied by dysfunction of NRG1/ErbB4 signaling and PV interneurons, and decreased theta and gamma oscillations. Notably, NRG1 treatment reversed LPS-induced decreases in p-ErbB4 and PV expressions, abnormalities in theta and gamma oscillations, and long-term memory decline. Together, our study demonstrated that dysfunction of NRG1/ErbB4 signaling in the hippocampus might mediate long-term memory decline in a mouse model of systemic inflammation induced by repeated LPS injections. Thus, targeting NRG1/ErbB4 signaling in the hippocampus may be promising for the prevention and treatment of this long-term memory decline., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the efficacy of ketochromate tromethamine and phloroglucinol combination therapy in early expulsion of ureteral calculi after extracorporeal shockwave lithotripsy (ESWL) in patients with distal ureteral clculi. The clinical and follow-up data of 275 patients with lower ureteral calculi who underwent ESWL were collected retrospectively in Civil Aviation General Hospital from January 1 st 2021 to June 30 th 2021. According to whether adjunctive medication used before ESWL patients were divided into control group and medication group (with ketochromate tromethamine 30 mg and phloroglucinol 80 mg before ESWL). Primary endpoint is the clearance rate of ureteral calculi after ESWL, secondary endpoint are the other outcomes and drug allergy. There were 138 cases in control group [117 were males and mean age (42±13) years]. Meanwhile, there were 137 cases in medication group [118 were males and mean age (42±12) years]. The clearance rate of ureteral calculi at 24 h (67.88% vs 48.55%, P= 0.001)、one week (76.64% vs 57.97%, P= 0.001) and four weeks (89.05% vs 76.08%, P =0.005)after ESWL in medication group were significant higher than that in control group. There was a significant difference in the VAS score of pain scale after ESWL (1.77±0.80 vs 2.06±1.04, P= 0.012) and re-ESWL rate (8.03% vs 17.39%, P =0.02) between two groups, but no difference with gross hematuria in 6 h after ESWL and drug allergy. Conclusions combination use of ketochromate tromethamine and phloroglucinol significantly improve early expulsion of ureteral calculi after ESWL in patients with distal ureteral calculi, with no side effect.

Background: Microglial activation-mediated neuroinflammation is one of the essential pathogenic mechanisms of sepsis-associated encephalopathy (SAE). Mounting evidence suggests that high mobility group box-1 protein (HMGB1) plays a pivotal role in neuroinflammation and SAE, yet the mechanism by which HMGB1 induces cognitive impairment in SAE remains unclear. Therefore, this study aimed to investigate the mechanism of HMGB1 underlying cognitive impairment in SAE., Methods: An SAE model was established by cecal ligation and puncture (CLP); animals in the sham group underwent cecum exposure alone without ligation and perforation. Mice in the inflachromene (ICM) group were continuously injected with ICM intraperitoneally at a daily dose of 10 mg/kg for 9 days starting 1 h before the CLP operation. The open field, novel object recognition, and Y maze tests were performed on days 14-18 after surgery to assess locomotor activity and cognitive function. HMGB1 secretion, the state of microglia, and neuronal activity were measured by immunofluorescence. Golgi staining was performed to detect changes in neuronal morphology and dendritic spine density. In vitro electrophysiology was performed to detect changes in long-term potentiation (LTP) in the CA1 of the hippocampus. In vivo electrophysiology was performed to detect the changes in neural oscillation of the hippocampus., Results: CLP-induced cognitive impairment was accompanied by increased HMGB1 secretion and microglial activation. The phagocytic capacity of microglia was enhanced, resulting in aberrant pruning of excitatory synapses in the hippocampus. The loss of excitatory synapses reduced neuronal activity, impaired LTP, and decreased theta oscillation in the hippocampus. Inhibiting HMGB1 secretion by ICM treatment reversed these changes., Conclusions: HMGB1 induces microglial activation, aberrant synaptic pruning, and neuron dysfunction in an animal model of SAE, leading to cognitive impairment. These results suggest that HMGB1 might be a target for SAE treatment., (© 2023. The Author(s).)

Sepsis-associated encephalopathy (SAE) is commonly defined as diffuse brain dysfunction and can manifest as delirium to coma. Accumulating evidence has suggested that perineuronal net (PNN) plays an important role in the modulation of the synaptic plasticity of central nervous system. We here investigated the role of PNN in SAE induced by lipopolysaccharide (LPS) injection. Behavioral tests were performed by open field, Y-maze, and fear conditioning tests at the indicated time points. The densities of vesicular γ-aminobutyric acid transporter, vesicular glutamate transporter 1, PNN, and parvalbumin (PV) in the hippocampus were evaluated by immunofluorescence. Matrix metalloproteinases-9 (MMP-9) expression and its activity were detected by Western blot and gel zymography, respectively. Local field potential was recorded by in vivo electrophysiology. LPS-treated mice displayed significant cognitive impairments, coincided with activated MMP-9, decreased PNN and PV densities, reduced inhibitory and excitatory input onto PV interneurons enwrapped by PNN, and decreased gamma oscillations in hippocampal CA1. Notably, MMP-9 inhibitor SB-3CT treatment rescued most of these abnormalities. Taken together, our study demonstrates that active MMP-9 mediated PNN remodeling, leading to reduced inhibitory and excitatory input onto PV interneurons and abnormal gamma oscillations in hippocampal CA1, which consequently contributed to cognitive impairments after LPS injection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery., Design: Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded., Methods: Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis., Results: Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p < 0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p < 0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p < 0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients., Conclusions: Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: 5-Hydroxymethylfurfural (5-HMF) is an important component of air pollution, confirmed to be a risk factor for pulmonary inflammation. However, its association with general health is unknown. This article aimed to clarify the effect and mechanism of 5-HMF in the occurrence and aggravation of frailty in mice by investigating whether exposure to 5-HMF was linked to the occurrence and aggravation of mice frailty., Methods: Twelve male C57BL/6 mice (12-month-old, 38 ± 1 g) were randomly divided into the control group and the 5-HMF group. The 5-HMF group was treated with 5-HMF (1 mg/kg/day, respiratory exposure) for 12 months, whereas the control group was treated with equal amounts of sterile water. After the intervention, the ELISA method was used to detect the serum inflammation level of the mice, and the physical performance and frail status were evaluated using a Fried physical phenotype-based assessment tool. The differences in the body compositions were calculated from their MRI images, and the pathological changes in their gastrocnemius muscle were revealed using the H&E staining. Furthermore, the senescence of skeletal muscle cells was evaluated by measuring the expression levels of senescence-related proteins by the western blotting., Results: In the 5-HMF group, serum inflammatory factors IL-6, TNF-α, and CRP levels were significantly raised ( p  < 0.01). Mice in this group had higher frailty scores and significantly reduced grip strength ( p  < 0.001), slower weight gains, less WVgastrocnemius muscle masses, and lower sarcopenia indices (SI). In addition, the cross-sectional areas of their skeletal muscles were reduced, and the levels of their cell senescence-related proteins (p53, p21, p16, SOD1, SOD2, SIRT1, SIRT3) were considerably altered ( p  < 0.01)., Conclusion: 5-HMF may induce chronic and systemic inflammation, which in turn accelerates the progression of the frailty of mice through cell senescence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment., Methods: Both female and male mice received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining., Results: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis., Conclusions: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe 2 O 3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe 2 O 3 , which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe 2 O 3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm 2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe 2 O 3 nanorod arrays (FT). The Hydrogen (H 2 ) production from PEC water splitting of Fe 2 O 3 was highly improved by Ce doping to achieve an evolution rate of 21 μmol/cm 2 /h.

Five-field 130° wide-angle imaging is the standard of care for retinopathy of prematurity (ROP) screening with an ideal hypothetical composite field-of-view (FOV) of 180°. We hypothesized that in many real-world scenarios the effective composite FOV is considerably less than ideal. This observational retrospective study analyzed the effective FOV of fundus photos of patients screened for ROP as part of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative. Five fundus photos were selected from each eye per image session. Effective FOV was defined as the largest circular area centered on the optic disc that encompassed retina in each of the four cardinal views. Seventy-three subjects were analyzed, 35 without ROP and 34 with ROP. Mean effective FOV was 144.55 ± 6.62° ranging from 130.00 to 153.71°. Effective FOV was not correlated with the presence or absence of ROP, gestational age, birth weight, or postmenstrual age. Mean effective FOV was wider in males compared to females. Standard five-field 130° fundus photos yielded an average effective FOV of 144.54° in the SUNDROP cohort. This implies that an imaging FOV during ROP screening considerably less than the hypothetical ideal of 180° is sufficient for detecting treatment warranted ROP., (© 2022. The Author(s).)

Four dinuclear bismuth(III) Schiff-base complexes bearing Schiff-base ligands have been synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analysis, and spectral techniques (FT-IR, NMR and MS). The analytical data reveal the bismuth(III) complexes possess 1:1 metal-ligand ratios. In vitro biological studies have revealed that bismuth(III) complexes displayed much higher antibacterial and antitumor activities than their parent ligands, which involves two gram-negative (S. aureus, B. subtili) and two gram-positive (E. coli, P. aeruginosa) bacteria, and human gastric cancer SNU-16 cells. The power-time curves of S. pombe exposed to tested compounds were detected by bio-microcalorimetry. Some thermokinetic parameters (k, P max, t G and Q total ) were derived based on the metabolic power-time curves, and their quantitative relationships with the concentrations (c) were further discussed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Postoperative delirium (POD), one of the most common complications following major surgery, imposes a heavy burden on patients and society. The objective of this exploratory study was to conduct a secondary analysis to identify whether there exist novel and reliable serum biomarkers for the prediction of POD., Methods: A total of 131 adult patients (≥ 65 years) undergoing lower extremity orthopedic surgery with were enrolled in this study. Cognitive function was assessed preoperatively with Mini-Mental State Examination (MMSE). Delirium was diagnosed according to the Confusion Assessment Method (CAM) criteria on preoperative day and postoperative days 1-3. The preoperative serum levels of a panel of 16 biochemical parameters were measured by ELISA., Results: Thirty-five patients developed POD, with an incidence of 26.7%. Patients in POD group were older (P = 0.001) and had lower preoperative MMSE scores (P = 0.001). Preoperative serum levels of prostaglandin E2 (PGE2, P < 0.001), S100β (P < 0.001), glial fibrillary acidic protein (P < 0.001) and neurofilament light (P = 0.002) in POD group were significantly increased. Logistic regression analysis showed that advanced age (OR = 1.144, 95%CI: 1.008 ~ 1.298, P = 0.037), higher serum neurofilament light (OR = 1.003, 95%CI: 1.000 ~ 1.005, P = 0.036) and PGE2 (OR = 1.031, 95%CI: 1.018 ~ 1.044, P < 0.001) levels were associated with the development of POD. In addition, serum level of PGE2 yielded an area under the ROC curve (AUC) of 0.897 to predict POD (P < 0.001), with a sensitivity of 80% and a specificity of 83.3%., Conclusions: Our study showed that higher preoperative serum PGE2 level might be a biomarker to predict the occurrence of POD in elderly patients undergoing elective orthopedic surgery., Trial Registration: NCT03792373 www., Clinicaltrials: gov ., (© 2022. The Author(s).)

Early life immune activation has negative effects on the development of central nervous system and cognitive function, yet the underlying mechanism remains unclear. Increasing evidence has demonstrated that inflammation induces changes in microglia morphology, which lead to excessive synaptic pruning and improper function of neural circuits. Therefore, we hypothesized that early immune activation induced microglia activation, contributing to synaptic and cognitive impairments in adolescent mice. To establish the animal model of early immune activation, pups received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal 10 (P10). Environmental enrichment (EE) was conducted four hours per day during P10-P38. Behavioral tests were performed by open field (P39), elevated plus-maze (P40) and Y maze tests (P41). The protein levels of glutamic acid decarboxylas67 (GAD67), parvalbumin (PV), vesicular gaba amino acid transporter (vGAT) and vesicular glutamate transporters (vGLUT1) were determined in the hippocampi and medial prefrontal cortex (mPFC). The protein levels of nuclear factor κB (NF-κB)/p65, NF-κB/p50, interleukin-1β (IL-1β), tumor necrosis factor - ɑ (TNF-ɑ) were determined in the hippocampi. The dendritic spine density was evaluated in the CA1 of the hippocampus. In our study, we showed that early life LPS exposure induced microglia activation and excessive inhibitory synapse engulfment, decreased number of perisomatic puncta on both inhibitory PV interneurons and excitatory neurons, which might contribute to excitation/inhibition imbalance, dendritic spine loss, and cognitive impairment in adolescent mice. Notably, EE rescued most of these abnormalities and improved cognitive impairment. In conclusion, our study demonstrated that reduced inhibition might contribute to early life LPS exposure induced-cognitive impairment. We also provided the possibility of the protective role of EE in rescuing these long-term adverse effects., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent evidence has shown that presenilin enhancer 2 (Pen2; Psenen) plays an essential role in corticogenesis by regulating the switch of apical progenitors (APs) to basal progenitors (BPs). The hippocampus is a brain structure required for advanced functions, including spatial navigation, learning and memory. However, it remains unknown whether Pen2 is important for hippocampal morphogenesis. To address this question, we generated Pen2 conditional knockout (cKO) mice, in which Pen2 is inactivated in neural progenitor cells (NPCs) in the hippocampal primordium. We showed that Pen2 cKO mice exhibited hippocampal malformation and decreased population of NPCs in the neuroepithelium of the hippocampus. We found that deletion of Pen2 neither affected the proliferative capability of APs nor the switch of APs to BPs in the hippocampus, and that it caused enhanced transition of APs to neurons. We demonstrated that expression of the Notch1 intracellular domain (N1ICD) significantly increased the population of NPCs in the Pen2 cKO hippocampus. Collectively, this study uncovers a crucial role for Pen2 in the maintenance of NPCs during hippocampal development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Patients undergoing coronary artery bypass graft (CABG) are at high risk for developing postoperative delirium (POD). A simple prediction rule may benefit patients from early identification of POD followed by adequate preventive strategies. The purpose of the current study was to develop and validate a POD prediction rule for patients undergoing CABG (POD-CABG), by considering all possible perioperative factors., Methods: In this prospective cohort study, patients who underwent first elective isolated CABG were continuously enrolled from May 2014 to November 2015 in a tertiary hospital. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Patients' perioperative risk factors were collected through interviews and review of medical records. The area under receiver-operating characteristic curve (AUC) was used to assess the overall performance of the predictive rule., Results: A total of 242 and 148 patients were enrolled in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified seven variables that were independently associated with POD: age (≥65 years), gender (female), history of myocardial infarction and diabetes mellitus, postoperative atrial fibrillation, the use of intra-aortic balloon pump, and serum interleukin-6 ≥478 pg/ml at 18 hours after surgery. The AUC of the POD-CABG was 0.84 (95% CI, 0.79-0.90) in the derivation cohort, and was 0.86 (95% CI, 0.80-0.91) after bootstrap resampling. The AUC was 0.81 (95% CI, 0.73-0.88) after the POD-CABG was applied to the validation cohort., Conclusions: The POD-CABG with inclusion of interleukin-6 demonstrated good performance in predicting POD., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest, (Copyright © 2021. Published by Elsevier Ltd.)

Preeclampsia remains a high cause of incidence and death for mothers and fetuses in developing nations. Preeclampsia has numerous clinical and biochemical markers that have been tested, but they have failed to provide a conclusive diagnosis in the different phases of the disease's progression. Herein, our team intended to determine potential diagnostic biomarkers for preeclampsia and analyzed associations with immune cells. Two microarray data from mankind's preeclampsia and control specimens were acquired from GSE75010 and GSE44711 datasets. Differentially expressed genes (DEGs) were identified between77 normal samples and 80 preeclampsia samples. Candidate biomarkers were discovered using the least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) analysis. The expressions and diagnostic values of genes in preeclampsia were further demonstrated in the GSE44711 dataset (8 control samples and 8 preeclampsia samples). The correlation of critical genes with the proportion of immune cells was analyzed. We identified 20 DEGs in preeclampsia. Diseases enriched by DEGs were mainly related to preeclampsia, gestational diabetes, ovarian disease, female reproductive system disease, and endocrine system disease. COL17A1, FLT1, FSTL3, and SERPINA3 were identified as diagnostic genes of preeclampsia and validated in the GSE44711 datasets. Immune cell infiltration assays suggested that COL17A1, FLT1, FSTL3, and SERPINA3 were related to several immune cells. Overall, we identified four critical diagnostic genes in preeclampsia. Furthermore, more well-designed research studies with larger cohorts were warranted to confirm the value of the four genes for the diagnosis and outcome of preeclampsia patients., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Mu-yi Yang et al.)

Few studies have investigated factors associated with acute postsurgical pain (APSP) trajectories, and whether the APSP trajectory can predict chronic postsurgical pain (CPSP) remains unclear. We aimed to identify the predictors of APSP trajectories in patients undergoing gastrointestinal surgery. Moreover, we hypothesised that APSP trajectories were independently associated with CPSP. We conducted a prospective cohort study of 282 patients undergoing gastrointestinal surgery to describe APSP trajectories. Psychological questionnaires were administered 1 day before surgery. Meanwhile, demographic characteristics and perioperative data were collected. Average pain intensity during the first 7 days after surgery was assessed by a numeric rating scale (NRS). Persistent pain intensity was evaluated at 3 and 6 months postoperatively by phone call interview. CPSP was defined as pain at the incision site or surrounding areas of surgery with a pain NRS score ≥ 1 at rest. The intercept and slope were calculated by linear regression using the least squares method. The predictors for the APSP trajectory and CPSP were determined using multiple linear regression and multivariate logistic regression, respectively. Body mass index, morphine milligram equivalent (MME) consumption, preoperative chronic pain and anxiety were predictors of the APSP trajectory intercept. Moreover, MME consumption and preoperative anxiety could independently predict the APSP trajectory slope. The incidence of CPSP at 3 and 6 months was 30.58% and 16.42% respectively. APSP trajectory and age were predictors of CPSP 3 months postoperatively, while female sex and preoperative anxiety were predictive factors of CPSP 6 months postoperatively. Preoperative anxiety and postoperative analgesic consumption can predict APSP trajectory. In addition, pain trajectory was associated with CPSP. Clinicians need to stay alert for these predictors and pay close attention to pain resolution., (© 2022. The Author(s).)

Treatment outcomes in retinopathy of prematurity (ROP) are closely correlated with the location (i.e. zone) of disease, with more posterior zones having poorer outcomes. The most posterior zone, Zone I, is defined as a circle centered on the optic nerve with radius twice the distance from nerve to fovea, or subtending an angle of 30 degrees. Because the eye enlarges and undergoes refractive changes during the period of ROP screening, the absolute area of Zone I according to these definitions may likewise change. It is possible that these differences may confound accurate assessment of risk in patients with ROP. In this study, we estimated the area of Zone I in relation to different ocular parameters to determine how variability in the size and refractive power of the eye may affect zoning. Using Gaussian optics, a model was constructed to calculate the absolute area of Zone I as a function of corneal power, anterior chamber depth, lens power, lens thickness, and axial length (AL), with Zone I defined as a circle with radius set by a 30-degree visual angle. Our model predicted Zone I area to be most sensitive to changes in AL; for example, an increase of AL from 14.20 to 16.58 mm at postmenstrual age 32 weeks was calculated to expand the area of Zone I by up to 72%. These findings motivate several hypotheses which upon future testing may help optimize treatment decisions for ROP., (© 2022. The Author(s).)

Background : The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the "first responders", play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified. Methods : In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed Kit W-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again. Results : Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate. Conclusion : Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Dong, Liu, Ji, Zhang, Dai, Sun, Liu, Zhou, Sha, Qian, Li, Yao and Li.)

Purpose: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging., Methods: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam., Results: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity., Conclusion: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.

Background: Regional anesthesia has been used to reduce acute postsurgical pain and to  prevent chronic pain. The best technique, however, remains controversial., Objectives: The aim of this study was to assess the short- and long-term postoperative analgesic efficacy of ultrasound-guided quadratus lumborum block (QLB) in open gastrointestinal surgery., Study Design: A randomized, double-blinded, controlled trial., Setting: Operating room; postoperative recovery room and ward., Methods: One hundred eighteen patients underwent elective gastrointestinal surgery randomly assigned into 2 groups (QLB group or control group). Before anesthetic induction, QLB was performed bilaterally under ultrasound guidance using 20 mL of 0.375% ropivacaine or saline solution at each abdominal wall. The primary outcome was cumulative oxycodone consumption within 24 h after surgery. The secondary outcomes were acute pain intensity, incidence of chronic pain, and incidence of postoperative nausea or vomiting (PONV), dizziness, and pruritus., Results: The cumulative oxycodone consumption was significantly lower in the QLB group during the first 6, 6-24, 24, and 48 h postoperatively when compared to the control group. At rest or during coughing, the numeric rating scale scores were significantly lower at 1, 3, 6, and 12 h postoperatively in the QLB group compared to the control group. There were no significant differences between the 2 groups regarding the incidence of chronic postoperative pain at 3 or 6 months after surgery. Significant differences were found in the incidence of PONV between the two groups, but other complications, such as dizziness and pruritus, did not differ significantly., Limitations: We did not confirm the QLB effectiveness with sensory level testing after local anesthetic injection. Cumulative oxycodone consumption could have been affected by the patients' use of oxycodone for nonsurgical pain., Conclusions: Ultrasound-guided QLB provided superior short-term analgesia and reduced oxycodone consumption and the incidence of PONV after gastrointestinal surgery. However, the incidence of chronic pain was not significantly affected by this anesthetic technique.

Background and Objective: This study aimed to identify the degree of concordance between fluorescein angiograms (FA) and fundus photographs (FP) in assessing the severity and potential need for treatment in infants 45 weeks or older postmenstrual age (PMA) with type 2 or less retinopathy of prematurity (ROP)., Patients and Methods: An observational retrospective case series performed at Associated Retinal Consultants, William Beaumont Hospital in Royal Oak, Michigan. All infants born between 2006 and 2016 with stage 1 to 3 ROP that did not meet type 1 ROP criteria (type 2 or less) who received ablative laser therapy during or after age 45 weeks PMA. Pretreatment FP and FA images were randomized and sent to nine expert retina specialist graders to assess severity and inter-grader variability., Results: A total of 10 babies (19 eyes) were enrolled in this study, and 53 FAs and 27 FPs of these 19 eyes were selected to be interpreted by the nine graders. The number of eyes deemed to be abnormal and warranted for treatment was higher with FA, whereas more eyes were deemed "normal" with FP., Conclusion: Although still controversial, knowledge of these findings may encourage retina specialists to closely examine infants with mild ROP older than age 45 weeks PMA and consider ablative laser therapy under certain conditions (even if not meeting type 1 Early Treatment for ROP criteria). [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:636-641.] .

Introduction: Focal choroidal excavation (FCE) is a concavity of the choroid detected on optical coherence tomography (OCT). It is usually idiopathic and the affected eyes are otherwise healthy with near-normal overlying retinal architecture and good visual acuity., Purpose: To report a case of bilateral conforming FCE in the setting of Stargardt disease and inactive ocular toxoplasmosis., Case Report: A 20-year-old man with known history of Stargardt disease, healed toxoplasmosis, and high myopia presented to our ophthalmology department for follow-up examination and was found with bilateral FCEs not present in any of his previous examinations., Conclusion: FCEs have been reported in the literature in otherwise healthy eyes as well as a broad spectrum of ocular diseases. The case herein reported Stargardt disease, toxoplasmosis, and high myopia all could potentially contribute to the pathogenesis of these findings. Further studies are needed to define etiologies as well as clinical significance and course of FCEs.