Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.     

Use of different combination diphtheria-tetanus-acellular pertussis vaccines does not increase risk of 30-day infant mortality. A population-based linkage cohort study using administrative data from the Australian Childhood Immunisation Register and the National Death Index.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

神经外科研究生就业率与培养情况分析——以北京市神经外科研究所为例

北京市神经外科研究所是国内培养神经外科人才的高端基地之一。近 10 年来，研究所培养了近 200名研究生，其中包括博士研究生 78 人，硕士研究生 120 人。通过对近 10 年来研究所硕士及博士研究生毕业就业情况梳理，分析三甲医院毕业生就业率、京内就业率、京外就业率及总体就业率情况，探讨提升研究所研究生培养质量的途径，以达到提高研究生核心竞争力的目的，以期对神经外科高层次的医学人才培养提供有益建议，为各级医疗卫生机构提供高层次的神经外科高端人才。     

Mechanisms of repigmentation induced by photobiomodulation therapy in vitiligo

Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low‐level laser light (coherent light) or light‐emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes. Since follicular melanoblasts (MBs) are derived from the melanocyte stem cells residing at the bulge area of hair follicle, the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low‐energy helium‐neon (He‐Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He‐Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O₂ consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He‐Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He‐Ne laser initiated mitochondrial retrograde signalling via a Ca²⁺‐dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic‐AMP response element binding protein)‐related cascade, is responsible for the He‐Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He‐Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.     

The effect of patient ethnicity on the accuracy of peripheral pulse oximetry in patients with COVID-19 pneumonitis: a single-centre,retrospective analysis

Pulse oximetry is used widely to titrate oxygen therapy and for triage in patients who are critically ill. However, there are concerns regarding the accuracy of pulse oximetry in patients with COVID-19 pneumonitis and in patients who have a greater degree of skin pigmentation. We aimed to determine the impact of patient ethnicity on the accuracy of peripheral pulse oximetry in patients who were critically ill with COVID-19 pneumonitis by conducting a retrospective observational study comparing paired measurements of arterial oxygen saturation measured by co-oximetry on arterial blood gas analysis (SaO₂) and the corresponding peripheral oxygenation saturation measured by pulse oximetry (S_pO₂). Bias was calculated as the mean difference between SaO₂ and S_pO₂ measurements and limits of agreement were calculated as bias ±1.96 SD. Data from 194 patients (135 White ethnic origin, 34 Asian ethnic origin, 19 Black ethnic origin and 6 other ethnic origin) were analysed consisting of 6216 paired SaO₂ and S_pO₂ measurements. Bias (limits of agreement) between SaO₂ and S_pO₂ measurements was 0.05% (−2.21–2.30). Patient ethnicity did not alter this to a clinically significant degree: 0.28% (1.79–2.35), −0.33% (−2.47–2.35) and −0.75% (−3.47–1.97) for patients of White, Asian and Black ethnic origin, respectively. In patients with COVID-19 pneumonitis, S_pO₂ measurements showed a level of agreement with SaO₂ values that was in line with previous work, and this was not affected by patient ethnicity.     

Associations between anthropometric indicators in early life and low-grade inflammation,insulin resistance and lipid profile in adolescence

Background and aimsThe long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence.Methods and resultsRetrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08 ± 1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents.ConclusionA high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes.     

Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.