Objective
Deep neck infection (DNI) associated with descending necrotizing mediastinitis (DNM) is a highly lethal condition. This retrospective review was performed to share our experience performing ...multidisciplinary management of DNI associated with DNM during a 7-year period.
Methods
We reviewed 16 patients who had been surgically treated for DNM at Peking Union Medical College Hospital from April 2010 to July 2017. The clinical outcomes were analysed to determine the most appropriate therapeutic strategy.
Results
Five women and 11 men were included in this study. Their mean age was 54.9 ± 14.3 years. DNM-associated infections most commonly occurred secondary to odontogenic infections (n = 10). Thirteen patients required tracheotomy because of tracheal compression. All patients underwent unilateral or bilateral cervicotomy. Six patients with DNM localized in the upper mediastinal space underwent transcervical mediastinal drainage, while 10 patients with DNM extending to the lower mediastinum were treated by cervicotomy and video-assisted thoracoscopic surgery. Three patients died of multiple organ failure.
Conclusion
Multidisciplinary treatment can achieve favourable outcomes in >80% of patients with DNM. Early diagnosis, proper airway management, and adequate surgical drainage are crucial for reducing mortality in patients with DNM, and minimally invasive procedures also play an important role.
Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. ...Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxietyand obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL– and not BLA– and vHipp–NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL–NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.
Exposure to benzo(a)pyrene (BaP) has been shown to cause mitochondrial dysfunction and injury to neural cells. Resveratrol (RSV) has been studied as an antioxidant, anti-inflammatory, anti-apoptotic, ...and anticancer agent and can modulate mitochondrial function in vitro and in vivo. However, the molecular mechanisms underlying RSV’s protection against mitochondrial dysfunction have not been fully elucidated. To investigate whether RSV can effectively prevent BaP-induced mitochondrial dysfunction, we tested the effects of RSV in primary neuronal models. Our results confirmed that neurons exhibited mitochondrial dysfunction and apoptosis in the mitochondrial pathway after BaP-treatment, and that pretreatment with RSV could reduce that dysfunction. Further, our results indicated that RSV pretreatment enhanced mitochondrial biogenesis via the AMPK/PGC-1α pathway and activated mitophagy via the PINK1-Parkin and AMPK/ULK1 pathways, thereby coordinating mitochondrial homeostasis. We also found that RSV could alleviate mitochondrial network fragmentation caused by BaP. This work provided insights into the role of RSV in preventing BaP-induced primary neuronal apoptosis in the mitochondrial pathway, mainly via regulation of mitochondrial biogenesis and mitophagy through AMPK pathway, thus maintaining the integrity of the mitochondrial network.
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•BaP can induce neuronal damage in mitochondrial apoptotic pathways.•RSV can relieve BaP-induced disruption of mitochondrial homeostasis.•RSV enhances mitochondrial biogenesis by AMPK/PGC-1α signaling pathway.•RSV regulates mitophagy via AMPK/ULK1 signaling pathway.
Oxidative stress is preferentially treated as a risk factor for the development and progression of osteoporosis. Corynoline as a component of Corydalis bungeana Turcz presents antioxidative and ...anti‐inflammatory properties. In the present study, the effects of Corynoline on osteoblasts following hydrogen peroxide (H2O2)‐induced injury were evaluated accompanied by the investigation of the molecular mechanisms involved. It was found that Corynoline downregulated the intracellular reactive oxygen species (ROS) generation and restored the osteogenic potential of the disrupted osteoblasts by H2O2 exposure. Furthermore, Corynoline was revealed to activate the Nrf2/HO‐1 signaling pathway, while ML385 (an Nrf2 inhibitor) would prevent the Corynoline‐mediated positive effects on the disrupted osteoblasts. In terms of the animal experiments, Corynoline treatment contributed to a significantly alleviated bone loss. These findings indicate that Corynoline may significantly attenuate the H2O2‐induced oxidative damage of osteoblasts via the Nrf2/HO‐1 signaling pathway, providing novel insights to the development of treatments for osteoporosis induced by oxidative injury.
Corynoline could upregulate the antioxidative enzyme expression in H2O2‐treated osteoblasts by activating the Nrf2 pathway, reducing the negative effect of oxidative stress, and strengthening the function of osteoblasts. The in vitro experiment results also showed that Corynoline delayed osteoporosis progression in the rat model and restored Nrf2 in situ expression. Overall, Corynoline could activate the Nrf2 pathway and mitigate or suppress osteoporosis‐related bone loss through the Nrf2 pathway, showing promise as a potential treatment for osteoporosis.
Abstract Developing dynamic color‐tunable ultra‐long room temperature phosphorescence (URTP) polymers with afterglow of over 1 s, photo‐chromism, and multi‐stimuli response for practical ...anti‐counterfeiting and information security applications is attractive but very challenging. Herein, by doping multicolor phosphorescence pyridinium bromide L block or viologen‐based photo‐chromic V block into polyvinyl alcohol matrixes, the water‐stimuli‐responsive color‐tunable URTP polymer films with afterglow of up to 8 s and the reversible viologen‐based photochromic polymer films have been developed. More significantly, a series of dynamic color‐tunable URTP polymer films with ultra‐long afterglow of over 6 s, photo‐chromism, and water‐stimuli response have been successfully exploited by integrating L and V blocks into one polymer system. Mechanistic investigations have revealed that their photo‐chromism mainly comes from the photo‐generated viologen free radicals. Furthermore, their dynamic multilevel anti‐counterfeiting applications have been demonstrated. These results pave the way to develop smarter multifunctional URTP materials for anti‐counterfeiting and optical sensing.
Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship ...with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.
Air pollutants are important contributors to cardiovascular diseases, but associations between long-term exposure to air pollutants and the risk of abdominal aortic aneurysm (AAA) are still unknown.
...This study was conducted using a sample of 449 463 participants from the UK Biobank. Hazard ratios and 95% confidence intervals for the risk of AAA incidence associated with long-term exposure to air pollutants were estimated using the Cox proportional hazards model with time-varying exposure measurements. Additionally, the cumulative incidence of AAA was calculated by using the Fine and Grey sub-distribution hazards regression model. Furthermore, this study investigated the combined effects and interactions between air pollutants exposure and genetic predisposition in relation to the risk of AAA onset.
Long-term exposure to particulate matter with an aerodynamic diameter <2.5 µm PM2.5, 1.21 (1.16, 1.27), particulate matter with an aerodynamic diameter <10 µm PM10, 1.21 (1.16, 1.27), nitrogen dioxide NO2, 1.16 (1.11, 1.22), and nitrogen oxides NOx, 1.10 (1.05, 1.15) was found to be associated with an elevated risk of AAA onset. The detrimental effects of air pollutants persisted even in participants with low-level exposure. For the joint associations, participants with both high levels of air pollutants exposure and high genetic risk had a higher risk of developing AAA compared with those with low concentrations of pollutants exposure and low genetic risk. The respective risk estimates for AAA incidence were 3.18 (2.46, 4.12) for PM2.5, 3.09 (2.39, 4.00) for PM10, 2.41 (1.86, 3.13) for NO2, and 2.01 (1.55, 2.61) for NOx.
In this study, long-term air pollutants exposure was associated with an increased risk of AAA incidence.
The natural lignin macromolecule is structurally complex and heterogeneous polymers. Herein, to comprehend the dynamic structural characteristics of poplar (Populus tomentosa) lignin during the ...growth stages, the native lignins were isolated from poplar woods with different growth stages (3, 6, and 18 months). Meanwhile, the microscopic distribution of lignin and structural features of components in the cell wall of poplar woods were monitored through CRM and CP/MAS 13C NMR, respectively. The isolated native lignin samples were synthetically characterized by NMR, GPC, and Py-GC/MS techniques for uncovering the structural variations of lignin during different growth stages. Solution-state 2D-HSQC NMR spectra of the poplar cell wall were also performed to investigate the structural characteristics of the cell wall components in poplar woods. All the results indicated that the lignin macromolecule was gradually polymerized with the increasing growth period of poplar. On the basis of the results obtained, possible structural models of the lignin macromolecule from different growth stages of poplar were proposed. The panoramic picture of chemical and structural characteristics of the lignin macromolecule is significant not only for the understanding of structural variations of the lignin macromolecule in the plant cell walls during different growth stages but also for biomass deconstruction and valorization.
Background
Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations.
Methods
We examined tumor tissue from a ...cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes.
Results
In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (
p
= 0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients.
Conclusions
MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.
Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this ...disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.
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