How do sphingosine-1-phosphate affect immune cells to resolve inflammation?

Inflammation is an important immune response of the body. It is a physiological process of self-repair and defense against pathogens taken up by biological tissues when stimulated by damage factors such as trauma and infection. Inflammation is the main cause of high morbidity and mortality in most diseases and is the physiological basis of the disease. Targeted therapeutic strategies can achieve efficient toxicity clearance at the inflammatory site, reduce complications, and reduce mortality. Sphingosine-1-phosphate (S1P), a lipid signaling molecule, is involved in immune cell transport by binding to S1P receptors (S1PRs). It plays a key role in innate and adaptive immune responses and is closely related to inflammation. In homeostasis, lymphocytes follow an S1P concentration gradient from the tissues into circulation. One widely accepted mechanism is that during the inflammatory immune response, the S1P gradient is altered, and lymphocytes are blocked from entering the circulation and are, therefore, unable to reach the inflammatory site. However, the full mechanism of its involvement in inflammation is not fully understood. This review focuses on bacterial and viral infections, autoimmune diseases, and immunological aspects of the Sphks/S1P/S1PRs signaling pathway, highlighting their role in promoting intradial-adaptive immune interactions. How S1P signaling is regulated in inflammation and how S1P shapes immune responses through immune cells are explained in detail. We teased apart the immune cell composition of S1P signaling and the critical role of S1P pathway modulators in the host inflammatory immune system. By understanding the role of S1P in the pathogenesis of inflammatory diseases, we linked the genomic studies of S1P-targeted drugs in inflammatory diseases to provide a basis for targeted drug development.

Recent advances in the study of anesthesia-and analgesia-related mechanisms of S-ketamine.

Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research.

The relationship between anesthesia and melatonin: a review.

Introduction: This comprehensive review delves into the intricate and multifaceted relationship between anesthesia and melatonin, aiming to provide essential insights for perioperative clinical anesthesiologists and stimulate interest in related research. Anesthesia and surgery have the potential to disrupt melatonin secretion, leading to sleep disorders, postoperative neurocognitive dysfunction and other symptoms. In comparison to previous reviews, this review provides a comprehensive summary of the various aspects linking melatonin and anesthesia, going beyond isolated perspectives. It explores the potential benefits of administering melatonin during the perioperative period, including alleviating anxiety, reducing pain, enhancing perioperative sleep quality, as well as demonstrating immunomodulatory and anti-tumor effects, potentially offering significant advantages for cancer surgery patients. Recent Findings: Anesthesia and surgery have a significant impact on melatonin secretion, the hormone crucial for maintaining circadian rhythms. These procedures disrupt the normal secretion of melatonin, leading to various adverse effects such as sleep disturbances, pain, and postoperative neurocognitive dysfunction. However, the administration of exogenous melatonin during the perioperative period has yielded promising results. It has been observed that perioperative melatonin supplementation can effectively reduce anxiety levels, improve pain management, enhance the quality of perioperative sleep, and potentially decrease the occurrence of postoperative delirium. In recent years, studies have found that melatonin has the potential to improve immune function and exhibit anti-cancer effects, further underscoring its potential advantages for patients undergoing cancer surgery. Summary: In summary, melatonin can serve as an adjuvant drug for anesthesia during the perioperative period. Its administration has demonstrated numerous positive effects, including anti-anxiety properties, sedation, analgesia, improved postoperative sleep, and the potential to reduce the incidence of postoperative delirium. Furthermore, its immune-modulating and anti-tumor effects make it particularly valuable for cancer surgery patients. However, further studies are required to determine the optimal dosage, long-term safety, and potential adverse reactions associated with melatonin administration.

Correlation Analysis of Prognostic Gene Expression, Tumor Microenvironment, and Tumor-Infiltrating Immune Cells in Ovarian Cancer.

Objective: Tumor microenvironment (TME) research can provide a crucial direction for the innovation and continuous improvement of novel biologic therapies for cancer. This study examined the relationship between the TME, expression profiles of the tumor-infiltrating immune cell, and prognostic gene expression in ovarian cancer (OC). Materials and Methods: Screening of CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG was performed using the bioinformatics methods. Results: All six genes were found to participate in immune-related molecular mechanisms and could regulate the expression of tumor-infiltrating cells. A Kaplan-Meier survival analysis results demonstrated a strong association between overall survival and all gene expressions in patients with OC. CIBERSORT analysis results showed that the expression level of all genes was positively correlated with γδ T cell proportions. Conclusion: Therefore, in the OC microenvironment, CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG can be potential immunotherapy targets and prognostic markers.

Role of sphingosine 1-phosphate (S1P) in sepsis-associated intestinal injury.

Sphingosine-1-phosphate (S1P) is a widespread lipid signaling molecule that binds to five sphingosine-1-phosphate receptors (S1PRs) to regulate downstream signaling pathways. Sepsis can cause intestinal injury and intestinal injury can aggravate sepsis. Thus, intestinal injury and sepsis are mutually interdependent. S1P is more abundant in intestinal tissues as compared to other tissues, exerts anti-inflammatory effects, promotes immune cell trafficking, and protects the intestinal barrier. Despite the clinical importance of S1P in inflammation, with a very well-defined mechanism in inflammatory bowel disease, their role in sepsis-induced intestinal injury has been relatively unexplored. In addition to regulating lymphocyte exit, the S1P-S1PR pathway has been implicated in the gut microbiota, intestinal epithelial cells (IECs), and immune cells in the lamina propria. This review mainly elaborates on the physiological role of S1P in sepsis, focusing on intestinal injury. We introduce the generation and metabolism of S1P, emphasize the maintenance of intestinal barrier homeostasis in sepsis, and the protective effect of S1P in the intestine. We also review the link between sepsis-induced intestinal injury and S1P-S1PRs signaling, as well as the underlying mechanisms of action. Finally, we discuss how S1PRs affect intestinal function and become targets for future drug development to improve the translational capacity of preclinical studies to the clinic.

Icariin reduces cognitive dysfunction induced by surgical trauma in aged rats by inhibiting hippocampal neuroinflammation.

Postoperative cognitive dysfunction (POCD) is a common postsurgical complication in elderly individuals, significantly impacting the quality of life of patients; however, there is currently no effective clinical treatment for POCD. Recent studies have shown that Icariin (ICA) has antiaging effects and improves cognitive function, but its effect in POCD has not been studied. In this study, we investigated the influence of ICA on cognitive function and the TLR4/NF-κB signaling pathway in a POCD rat model. We found that ICA reduced surgery-induced memory impairment, decreased hippocampal inflammatory responses, ameliorated neuronal injury in the hippocampus and inhibited microglial activation. In addition, we also observed that ICA inhibited activation of the TLR4/NF-κB signaling pathway. In summary, our research suggest that ICA can ameliorate surgery-induced memory impairment and that the improvements resulting from administration of ICA may be associated with inhibition of hippocampal neuroinflammation. Our research findings also provide insight into potential therapeutic targets and methods for POCD.

Erratum to "Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model".

[This corrects the article on p. 336 in vol. 7, PMID: 27493838.].

The potential value of exosomes as adjuvants for novel biologic local anesthetics.

The side effects of anesthetic drugs are a key preoperative concern for anesthesiologists. Anesthetic drugs used for general anesthesia and regional blocks are associated with a potential risk of systemic toxicity. This prompted the use of anesthetic adjuvants to ameliorate these side effects and improve clinical outcomes. However, the adverse effects of anesthetic adjuvants, such as neurotoxicity and gastrointestinal reactions, have raised concerns about their clinical use. Therefore, the development of relatively safe anesthetic adjuvants with fewer side effects is an important area for future anesthetic drug research. Exosomes, which contain multiple vesicles with genetic information, can be released by living cells with regenerative and specific effects. Exosomes released by specific cell types have been found to have similar effects as many local anesthetic adjuvants. Due to their biological activity, carrier efficacy, and ability to repair damaged tissues, exosomes may have a better efficacy and safety profile than the currently used anesthetic adjuvants. In this article, we summarize the contemporary literature about local anesthetic adjuvants and highlight their potential side effects, while discussing the potential of exosomes as novel local anesthetic adjuvant drugs.

Association of insulin resistance with bone mineral density in a nationwide health check-up population in China.

INTRODUCTION: Insulin resistance (IR) is closely associated with cardio-metabolic diseases. However, the impact of IR on bone mass remains obscure. The present study is to evaluate the association between the triglyceride-glucose (TyG) indicated IR and bone mass in a nationwide health check-up population in China. METHODS: We conducted a retrospective cross-sectional study including 788,247 participants and a longitudinal cohort study in 8770 participants who had repeated measurements of TyG index and bone mass in at least a 2-year follow-up period. The restricted cubic splines and logistic models were used to analyze the association between IR and bone mass in the cross-sectional study. The Cox model was applied to evaluate the relationship between baseline IR and the subsequent incidence of low bone mass and osteoporosis in the longitudinal study. RESULTS: In the cross-sectional study, the TyG index had positive correlations with low bone mass, osteoporosis, or both after adjusting for confounding factors (all P < 0.001). In the longitudinal cohort study, the baseline TyG index was significantly associated with the incidence of low bone mass, osteoporosis, or both during the follow-up period, with hazard ratios (HRs) of 1.56 (95 % confidence interval [CI]: 1.25, 1.93, P < 0.05), 1.66 (95%CI: 1.06, 2.59, P < 0.05), and 1.55 (95%CI: 1.27, 1.88, P < 0.05) after adjusting for confounding factors, respectively. CONCLUSIONS: These results suggest that IR indicated by TyG is significantly associated with an increased risk of low bone mass and osteoporosis. Therefore, bone mass monitoring and early prevention strategies may be needed in individuals with IR to prevent the occurrence of low bone mass and osteoporosis.

The increasing incidence and high body mass index-related burden of gallbladder and biliary diseases-A results from global burden of disease study 2019.

Background: Gallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide. Methods: Data on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change. Results: The global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05-679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21-742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25-49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases. Conclusion: The global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25-49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.

Transcutaneous electrical acupoint stimulation for reducing cognitive dysfunction in lumbar spine surgery: A randomized, controlled trail.

Objective: This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients with lumbar spine surgery. Methods: Older patients (aged 60-80 years old) receiving lumbar spine surgery under general anesthesia were randomly divided into group A, 3-day intervention group; group B, 7-day intervention group; control group C, sham TEAS group, selected "Baihui" (GV 20) and "Dazhui" (GV 14) point was intervened once 30 min before operation with "HANS" transcutaneous electrical stimulation device, and then once a day after operation for 30 min each time. The primary outcome was the incidence of postoperative cognitive impairment assessed by the use of the Mini Mental Rating Scale (MMSE), patients developed POCD according to the Z score method. The secondary outcome was serum interleukin-6 (IL-6), tumor Necrosis factor α (TNF-α), neuron-specific enolase (NSE), and S100ß protein levels. Results: Three days after surgery, the incidence of POCD in groups A((22.4%)) and B ((18.3%)) were lower than those in group C ((42.9%)) (P < 0.05). There was no significant difference between groups A and B (P > 0.05). Seven days after surgery, the incidence of POCD in group B (18.3%) was lower than that in groups A (26.5%) and B (42.9%), and the comparison between groups B and C was statistically significant (P < 0.05). On the 3rd and 7th days after surgery, the levels of IL-6, TNF-α, NSE, and S100ß in the two TEAS groups were lower than those in the sham TEAS group (P < 0.01), but higher than the preoperative levels in the three groups (P < 0.01). Conclusion: It seems that Perioperative TEAS intervention could reduce the level of inflammatory factors IL-6, TNF-α in the blood of older patients with lumbar spine surgery, and reduce the incidence of POCD. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200063030.

Assessment of corneal biomechanics in anisometropia using Scheimpflug technology.

Purpose: To investigate the relationship between corneal biomechanical and ocular biometric parameters, and to explore biomechanical asymmetry between anisometropic eyes using the corneal visualization Scheimpflug technology device (Corvis ST). Methods: 180 anisometropic participants were included. Participants were divided into low (1.00≤△Spherical equivalent (SE) < 2.00D), moderate (2.00D≤△SE < 3.00D) and high (△SE ≥ 3.00D) anisometropic groups. Axial length (AL), keratometry, anterior chamber depth (ACD) and corneal biomechanical parameters were assessed using the OA-2000 biometer, Pentacam HR and Corvis ST, respectively. Results: The mean age of participants was 16.09 ± 5.64 years. Stress-Strain Index (SSI) was positively correlated with SE (r = 0.501, p < 0.001) and negatively correlated with AL (r = -0.436, p < 0.001). Some other Corvis ST parameters had weak correlation with SE or AL. Corneal biomechanical parameters except for time of first applanation (A1T), length of second applanation (A2L), deformation amplitude (DA), first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) were correlated with ametropic parameters (SE or AL) in multiple regression analyses. A1T, velocity of first applanation (A1V), time of second applanation (A2T), A2L, velocity of second applanation (A2V), corneal curvature radius at highest concavity (HCR), peak distance (PD), DA, deformation amplitude ratio max (2 mm) (DAR), SPA1, integrated radius (IR), and SSI showed significant differences between fellow eyes (p < 0.05). There was no significant difference in asymmetry of corneal biomechanics among the three groups (p > 0.05). Asymmetry of some biomechanical parameters had weak correlation with asymmetry of mean corneal curvatures and ACD. However, asymmetry of corneal biomechanical parameters was not correlated with asymmetry of SE or AL (p > 0.05). Conclusion: More myopic eyes had weaker biomechanical properties than the contralateral eye in anisometropia. However, a certain linear relationship between anisometropia and biomechanical asymmetry was not found.

The global disease burden attributable to a diet low in fibre in 204 countries and territories from 1990 to 2019.

OBJECTIVE: The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019. DESIGN: All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review. SETTING: All data sourced from the GBD Study 2019. PARTICIPANTS: All age groups for both sexes. RESULTS: The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe. CONCLUSIONS: The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.

Percutaneous Endoscopic Discectomy Via a Transforaminal Approach for L5/S1 Far-Lateral Disc Herniation Assisted by Intraoperative Computed Tomography.

OBJECTIVE: To examine the clinical outcomes of a percutaneous lumbar transforaminal endoscopic discectomy (PTED) with intraoperative computed tomography (iCT) navigation for the treatment of L5-S1 far-lateral lumbar disc herniation (LDH). METHODS: A total of 30 patients with L5-S1 far-lateral LDH who underwent PTED with iCT navigation from September 2016 to October 2020 were enrolled in this study. Outcomes were assessed using the visual analog scale pain score, the Oswestry Disability Index, the Japanese Orthopedic Association score, the EQ-5D-5 L and the modified Macnab criteria. Preoperative and postoperative complications were recorded. RESULTS: The mean visual analog scale score for leg pain improved from 8.1 at baseline to 2.3, 0.9, 0.7 and 0.9 at 1 day, 1 week, 6 months, and 12 months postoperatively, respectively (P < 0.01). The mean Oswestry Disability Index improved from 78.1% at baseline to 45.5%, 21.9%, 12.6%, and 11.7% at 1 week, 1 month, 6 months, and 12 months postoperatively, respectively (P < 0.01); and the mean Japanese Orthopedic Association score improved from 8.6 at baseline to 14.2, 20.2, 24.4, and 25.6 at 1 day, 1 week, 6 months, and 12 months postoperatively, respectively (P < 0.01). At 12 months postoperatively, the EQ-5D-5 L value significantly increased, from -0.061 ± 0.138 to 0.903 ± 0.064. The rate of a good or excellent modified Macnab result was 93% (26/28) at 12 months postoperatively. In the present study, combined L5-S1 foraminal stenosis tended to lead poor outcomes, which required more postsurgical treatments. CONCLUSIONS: With iCT navigation, PTED is a feasible and effective minimally invasive surgery for L5-S1 far-lateral LDH.

Novel Thermosensitive Hydrogel Promotes Spinal Cord Repair by Regulating Mitochondrial Function.

The repair of spinal cord injury (SCI) is still a tough clinical challenge and needs innovative therapies. Mitochondrial function is significantly compromised after SCI and has emerged as an important factor causing neuronal apoptosis and hindering functional recovery. In this study, umbilical cord mesenchymal stem cells (UCMSC), which are promising seed cells for nerve regeneration, and basic fibroblast growth factor (bFGF) that have been demonstrated to have a variety of effects on neural regeneration were jointly immobilized in extracellular matrix (ECM) and heparin-poloxamer (HP) to create a polymer bioactive system that brings more hope and possibility for the treatment of SCI. Our results in vitro and in vivo showed that the UCMSC-bFGF-ECM-HP thermosensitive hydrogel has good therapeutic effects, mainly in reducing apoptosis and improving the mitochondrial function. It showed promising utility for the functional recovery of impaired mitochondrial function by promoting mitochondrial fusion, reducing pathological mitochondrial fragmentation, increasing mitochondrial energy supply, and improving the metabolism of MDA, LDH, and ROS. In addition, we uncovered a distinct molecular mechanism underlying the protective effects associated with activating p21-activated kinase 1 (PAK1) and mitochondrial sirtuin 4 (SIRT4) by the UCMSC-bFGF-ECM-HP hydrogel. The expansion of new insights into the molecular relationships between PAK1 and SIRT4, which links the mitochondrial function in SCI, can lay the foundation for future applications and help to provide promising interventions of stem-cell-based biological scaffold therapies and potential therapeutic targets for the clinical formulation of SCI treatment strategies.

Reliability and agreement of the central and mid-peripheral corneal thickness measured by a new Scheimpflug based imaging.

BACKGROUND: To assess the intra-observer repeatability and inter-observer reproducibility of central corneal thickness (CCT) and mid-peripheral corneal thickness (MPCT) measurements using a new Scheimpflug imaging instrument (Scansys) and compare the agreement with the rotating Scheimpflug corneal tomographer (Pentacam HR). METHODS: The same well-trained operator performed the measuring using the two devices, after which Scansys measurements were repeated by another operator. Both instruments required three consecutive measurements per subject. Corneal thickness measurements were obtained by each instrument, including CCT, thinnest corneal thickness (TCT), pupil corneal thickness (PCT), and MPCT. Test-retest repeatability (TRT), within-subject coefficient of variation (CoV), and intra-class correlation coefficient (ICC) were used to evaluate repeatability and reproducibility. A paired t-test was used to compare the differences between Scansys and Pentacam, and the agreement was compared with Bland-Altman plots. RESULTS: This study enrolled 112 healthy subjects. The CoV were <0.91% and 0.55% for repeatability and reproducibility, respectively. The ICC was close to 1 in all measurements. For intra-observer repeatability in the CT2mm region, TRT was <10.30 µm. Moreover, TRT was <15.26 µm within the CT5mm region. The paired t-test showed significant differences in all corneal thickness measurements (P<0.001). The central region and CT2mm agreement were high, but the largest range of 95% limits of agreement (LoA) appeared in the CTnasal-5mm. CONCLUSIONS: The new Scheimpflug imaging instrument showed excellent intra-observer repeatability and inter-observer reproducibility for corneal thickness measurements. The agreement analysis suggested that Scansys and Pentacam could be interchangeably used between the central region and CT2mm, except CT5mm.

Comparison of Anterior Ocular Biometric Measurements Using Swept-Source and Time-Domain Optical Coherence Tomography.

PURPOSE: To compare central corneal thickness (CCT), aqueous depth (AQD), and anterior chamber depth (ACD) measurements using the swept-source (CASIA SS-1000, Tomey, Japan) and time-domain (Visante, Carl Zeiss Meditec, USA) anterior segment optical coherence tomographers (OCT) in normal eyes. METHODS: Sixty-eight eyes of 68 subjects were included. Three consecutive scans of each subject were obtained using both devices in a random order by one experienced operator. Standard deviation (S w), coefficient of repeatability (CoR), coefficients of variation (CoV), and intraclass correlation coefficients (ICC) were used to evaluate the intraoperator repeatability. Agreement was assessed using the Bland-Altman plots and 95% limits of agreement (LoA). RESULTS: All measurements of the swept-source OCT (SS-OCT) and time-domain OCT (TD-OCT) showed high repeatability with low CoR (CCT: 2.34 µm and 6.16 µm; AQD: 0.05 mm and 0.09 mm; ACD: 0.06 mm and 0.09 mm), low CoV (CCT: 0.16% and 0.42%; AQD: 0.61% and 0.97%; ACD: 0.53% and 0.83%), and high ICC (>0.98). The mean CCT with SS-OCT was slightly thicker than the results with TD-OCT (difference = 4.55 ± 2.62 µm, P < 0.001). There was no statistically significant difference in AQD or ACD measurements between the two devices (0.01 ± 0.05 mm, P=0.111; 0.02 ± 0.05 mm, P=0.022, respectively). The 95% LoA between the SS-OCT and TD-OCT were -0.59 to 9.69 µm for CCT, -0.10 to 0.12 mm for AQD, and -0.09 to 0.12 mm for ACD. CONCLUSIONS: High levels of repeatability and agreement were found between the two devices for all three parameters, suggesting interchangeability. SS-OCT demonstrated superior repeatability compared with TD-OCT.

Agreement Between Two Optical Biometers Based on Large Coherence Length SS-OCT and Scheimpflug Imaging/Partial Coherence Interferometry.

PURPOSE: To evaluate the agreement between measurements obtained with a new optical biometer (Argos; Movu Inc) using large coherence length swept-source optical coherence tomography (SS-OCT) and those obtained with an optical biometer with a rotating Scheimpflug camera, combined with partial coherence interferometry (PCI) (Pentacam AXL; Oculus Optikgeräte GmbH) in adults. METHODS: The following measurements were examined and evaluated: axial length, central corneal thickness (CCT), anterior chamber depth (ACD), mean keratometry, J0 and J45 vectors, and corneal diameter. Measurements with the two biometers were conducted in triplicate per instrument in a random order by the same examiner. Paired t tests were employed to compare the difference between the two devices. The Bland-Altman method was implemented to assess their agreement. RESULTS: A total of 145 patients were enrolled in the study. The differences between the Scheimpflug/PCI-based biometer and the SS-OCT biometer were as follows: -0.02 ± 0.05 mm for axial length, 1.15 ± 5.79 µm for CCT, -0.04 ± 0.04 mm for ACD, -0.28 ± 0.16 diopters (D) for mean keratometry, 0.01 ± 0.11 D for J0, -0.02 ± 0.10 D for J45, and -1.03 ± 0.62 mm for corneal diameter. Bland-Altman plots showed narrow ranges in axial length, CCT, ACD, mean keratometry, and J0 and J45, which implied excellent agreement between the two biometers. Corneal diameter displayed poor agreement, with a 95% limits of agreement ranging from -2.25 to 0.19 mm. CONCLUSIONS: Excellent agreement was established between the measurements provided by the new optical biometer based on SS-OCT and the optical biometer using Scheimpflug imaging and PCI, except for corneal diameter. [J Refract Surg. 2020;36(7):459-465.].

Thermosensitive heparin-poloxamer hydrogel encapsulated bFGF and NGF to treat spinal cord injury.

The application of growth factors (GFs) for treating chronic spinal cord injury (SCI) has been shown to promote axonal regeneration and functional recovery. However, direct administration of GFs is limited by their rapid degradation and dilution at the injured sites. Moreover, SCI recovery is a multifactorial process that requires multiple GFs to participate in tissue regeneration. Based on these facts, controlled delivery of multiple growth factors (GFs) to lesion areas is becoming an attractive strategy for repairing SCI. Presently, we developed a GFs-based delivery system (called GFs-HP) that consisted of basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and heparin-poloxamer (HP) hydrogel through self-assembly mode. This GFs-HP was a kind of thermosensitive hydrogel that was suitable for orthotopic administration in vivo. Meanwhile, a 3D porous structure of this hydrogel is commonly used to load large amounts of GFs. After single injection of GFs-HP into the lesioned spinal cord, the sustained release of NGF and bFGF from HP could significantly improve neuronal survival, axon regeneration, reactive astrogliosis suppression and locomotor recovery, when compared with the treatment of free GFs or HP. Moreover, we also revealed that these neuroprotective and neuroregenerative effects of GFs-HP were likely through activating the phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling pathways. Overall, our work will provide an effective therapeutic strategy for SCI repair.

Valproic acid affects neuronal fate and microglial function via enhancing autophagic flux in mice after traumatic brain injury.

In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double-edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme-linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI-induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3-methyladenine partially abolished VPA-induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI-induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI. Cover Image for this issue: doi: 10.1111/jnc.14755.