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1.
Chem Commun (Camb) ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291575

RESUMEN

We discovered that employing inappropriate calibration curves for activity evaluation resulted in false positive results. Specifically, an artificial efficiency of hydrogen production is exaggerated by up to 2.2-fold if the calibration curves are misused, leading to considerably high false positive results. Our study highlights the importance of utilizing the correct calibration curve to ensure a true performance, and is beneficial for fostering advancements in the development of thermal-assisted photocatalysis.

2.
Angew Chem Int Ed Engl ; 63(39): e202410145, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-38979674

RESUMEN

Tuning the selectivity of CO2 electroreduction reaction (CO2RR) solely by changing electrolyte is a very attractive topic. In this study, we conducted CO2RR in different aqueous electrolytes over bulk metal electrodes. It was discovered that controlled CO2RR could be achieved by modulating cations in the electrochemical double layer. Specifically, ionic liquid cations in the electrolyte significantly inhibits the hydrogen evolution reaction (HER), while yielding high Faraday efficiencies toward CO (FECO) or formate (FEformate) depending on the alkali metal cations. For example, the product could be switched from CO (FECO=97.3 %) to formate (FEformate=93.5 %) by changing the electrolyte from 0.1 M KBr-0.5 M 1-octyl-3-methylimidazolium bromide (OmimBr) to 0.1 M CsBr-0.5 M OmimBr aqueous solutions over pristine Cu foil electrode. In situ spectroscopy and theoretical calculations reveal that the ordered structure generated by the assembly of Omim+ under an applied negative potential alters the hydrogen bonding structure of the interfacial water, thereby inhibiting the HER. The difference in selectivity in the presence of different cations is attributed to the hydrogen bonding effect caused by Omim+, which alters the solvated structure of the alkali metal cations and thus affects the stabilization of intermediates of different pathways.

3.
Immunol Res ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814567

RESUMEN

Natural killer T (NKT) cells are amongst the most important innate immune cells against hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1+ expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1+ monocytes in regulating the function of iNKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1+ monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with iNKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in the regulation of NKT cell function. We observed that the percentage of iNKT cells and CD4-iNKT cells gradually decreased, whereas the percentage of CCR2+TREM-1+ monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of iNKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of iNKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections.

4.
Adv Mater ; 36(15): e2308915, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38229552

RESUMEN

Nanotechnology profoundly affects the advancement of medicine. Limitations in diagnosing and treating cancer and chronic diseases promote the growth of nanomedicine. However, there are very few analytical and descriptive studies regarding the trajectory of nanomedicine, key research powers, present research landscape, focal investigative points, and future outlooks. Herein, articles and reviews published in the Science Citation Index Expanded of Web of Science Core Collection from first January 2000 to 18th July 2023 are analyzed. Herein, a bibliometric visualization of publication trends, countries/regions, institutions, journals, research categories, themes, references, and keywords is produced and elaborated. Nanomedicine-related academic output is increasing since the COVID-19 pandemic, solidifying the uneven global distribution of research performance. While China leads in terms of publication quantity and has numerous highly productive institutions, the USA has advantages in academic impact, commercialization, and industrial value. Nanomedicine integrates with other disciplines, establishing interdisciplinary platforms, in which drug delivery and nanoparticles remain focal points. Current research focuses on integrating nanomedicine and cell ferroptosis induction in cancer immunotherapy. The keyword "burst testing" identifies promising research directions, including immunogenic cell death, chemodynamic therapy, tumor microenvironment, immunotherapy, and extracellular vesicles. The prospects, major challenges, and barriers to addressing these directions are discussed.


Asunto(s)
Nanomedicina , Neoplasias , Humanos , Pandemias , Nanotecnología , Bibliometría , Microambiente Tumoral
5.
Nat Commun ; 14(1): 6971, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37914707

RESUMEN

Metallosalen-covalent organic frameworks have recently gained attention in photocatalysis. However, their use in CO2 photoreduction is yet to be reported. Moreover, facile preparation of metallosalen-covalent organic frameworks with good crystallinity remains considerably challenging. Herein, we report a series of metallosalen-covalent organic frameworks produced via a one-step synthesis strategy that does not require vacuum evacuation. Metallosalen-covalent organic frameworks possessing controllable coordination environments of mononuclear and binuclear metal sites are obtained and act as photocatalysts for tunable syngas production from CO2. Metallosalen-covalent organic frameworks obtained via one-step synthesis exhibit higher crystallinity and catalytic activities than those obtained from two-step synthesis. The optimal framework material containing cobalt and triazine achieves a syngas production rate of 19.7 mmol g-1 h-1 (11:8 H2/CO), outperforming previously reported porous crystalline materials. This study provides a facile strategy for producing metallosalen-covalent organic frameworks of high quality and can accelerate their exploration in various applications.

6.
J Am Chem Soc ; 145(44): 23905-23909, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37890007

RESUMEN

Selective oxidation of benzylic C-H to benzylic alcohols is a well-known challenge in the chemical community since benzylic C-H is more prone to be overoxidized to benzylic ketones. In this work, we report the highly selective electro-oxidation of benzylic C-H to benzylic alcohols in an undivided cell in ionic liquid-based solution. As an example, the selectivity toward xanthydrol could be as high as 95.7% at complete conversion of xanthene, a typical benzylic C-H compound, on gram-scale in imidazolium bromide/H2O/DMF. Mechanism investigation reveals that the imidazolium radical generated in situ participants in a proton-coupled electron transfer process and low-barrier hydrogen bonds stabilize the reaction intermediates, together steering the redox equilibrium, favoring benzylic alcohols over benzylic ketones.

7.
Front Neural Circuits ; 17: 1185095, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37396397

RESUMEN

Background: How volatile anesthetics work remains poorly understood. Modulations of synaptic neurotransmission are the direct cellular mechanisms of volatile anesthetics in the central nervous system. Volatile anesthetics such as isoflurane may reduce neuronal interaction by differentially inhibiting neurotransmission between GABAergic and glutamatergic synapses. Presynaptic voltage-dependent sodium channels (Nav), which are strictly coupled with synaptic vesicle exocytosis, are inhibited by volatile anesthetics and may contribute to the selectivity of isoflurane between GABAergic and glutamatergic synapses. However, it is still unknown how isoflurane at clinical concentrations differentially modulates Nav currents between excitatory and inhibitory neurons at the tissue level. Methods: In this study, an electrophysiological recording was applied in cortex slices to investigate the effects of isoflurane on Nav between parvalbumin (PV+) and pyramidal neurons in PV-cre-tdTomato and/or vglut2-cre-tdTomato mice. Results: Isoflurane at clinically relevant concentrations produced a hyperpolarizing shift in the voltage-dependent inactivation and slowed the recovery time from the fast inactivation in both cellular subtypes. Since the voltage of half-maximal inactivation was significantly depolarized in PV+ neurons compared to that of pyramidal neurons, isoflurane inhibited the peak Nav currents in pyramidal neurons more potently than those of PV+ neurons (35.95 ± 13.32% vs. 19.24 ± 16.04%, P = 0.036 by the Mann-Whitney test). Conclusions: Isoflurane differentially inhibits Nav currents between pyramidal and PV+ neurons in the prefrontal cortex, which may contribute to the preferential suppression of glutamate release over GABA release, resulting in the net depression of excitatory-inhibitory circuits in the prefrontal cortex.


Asunto(s)
Anestésicos por Inhalación , Isoflurano , Canales de Sodio Activados por Voltaje , Ratones , Animales , Isoflurano/farmacología , Parvalbúminas , Anestésicos por Inhalación/farmacología , Neuronas , Células Piramidales/fisiología , Corteza Prefrontal
8.
Front Immunol ; 14: 1155181, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969223

RESUMEN

Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.


Asunto(s)
Enfermedades Autoinmunes , Hemofilia A , Penfigoide Ampolloso , Humanos , Anciano , Vesícula , Autoanticuerpos
9.
Front Immunol ; 13: 950782, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36081499

RESUMEN

Colorectal cancer (CRC) is one of the most fatal cancers of the digestive system. Although cancer stem cells and metabolic reprogramming have an important effect on tumor progression and drug resistance, their combined effect on CRC prognosis remains unclear. Therefore, we generated a 21-gene mRNA stemness index-related metabolic risk score model, which was examined in The Cancer Genome Atlas and Gene Expression Omnibus databases (1323 patients) and validated using the Zhongshan Hospital cohort (200 patients). The high-risk group showed more immune infiltrations; higher levels of immunosuppressive checkpoints, such as CD274, tumor mutation burden, and resistance to chemotherapeutics; potentially better response to immune therapy; worse prognosis; and advanced stage of tumor node metastasis than the low-risk group. The combination of risk score and clinical characteristics was effective in predicting overall survival. Zhongshan cohort validated that high-risk score group correlated with malignant progression, worse prognosis, inferior adjuvant chemotherapy responsiveness of CRC, and shaped an immunoevasive contexture. This tool may provide a more accurate risk stratification in CRC and screening of patients with CRC responsive to immunotherapy.


Asunto(s)
Neoplasias Colorrectales , Aprendizaje Automático , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Pronóstico , Factores de Riesgo
10.
Front Oncol ; 12: 943423, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35965545

RESUMEN

Background: The correlation between high white blood cell (WBC) count and poor prognosis has been identified in various types of cancer; however, the clinical significance and immune context of WBC count in colorectal cancer remains unclear. Methods: Between February 2009 and November 2014, 7,433 patients at the Shanghai Cancer Center who had undergone elective surgery for colorectal cancer were enrolled in this retrospective cohort study. Patients were divided into two groups: low and high preoperative WBC groups. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan-Meier method and Cox regression analysis were used to identify independent prognostic factors in colorectal cancer patients. Tumor-infiltrating immune cells in the high and low preoperative WBC groups were compared using immunohistochemical staining. Results: Of the 7,433 patients who underwent colorectal cancer surgery and were available for analysis, 5,750 were included in the low preoperative WBC group, and 1,683 were included in the high preoperative WBC group. After propensity score matching, 1,553 patients were included in each group. Kaplan-Meier survival curves showed that a high preoperative WBC count was associated with a decreased overall survival (P = 0.002) and disease-free survival (P = 0.003), and that preoperative WBC count was an independent risk factor for overall survival (hazard ratio, 1.234; 95% confidence interval, 1.068-1.426; P = 0.004) and disease-free survival (hazard ratio, 1.210; 95% confidence interval, 1.047-1.397, P = 0.01). Compared to the low preoperative WBC group, the high preoperative WBC group exhibited higher expression of regulatory T cells (P = 0.0034), CD68+ macrophages (P = 0.0071), and CD66b+ neutrophils (P = 0.0041); increased expression of programmed cell death protein 1 (P = 0.005) and programmed cell death ligand 1 (P = 0.0019); and lower expression of CD8+ T cells (P = 0.0057) in colorectal cancer patients. Conclusions: Our research indicates that a high preoperative WBC count is a prognostic indicator in colorectal cancer patients and is associated with an immunosuppressive tumor microenvironment, which could aid in future risk stratification.

11.
Front Behav Neurosci ; 16: 837523, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35401134

RESUMEN

Normal neurodevelopment requires precise expression of the key ubiquitin ligase gene Ube3a. Comparing newly generated mouse models for Ube3a downregulation (models of Angelman syndrome) vs. Ube3a upregulation (models for autism), we find reciprocal effects of Ube3a gene dosage on phenotypes associated with circadian rhythmicity, including the amount of locomotor activity. Consistent with results from neurons in general, we find that Ube3a is imprinted in neurons of the suprachiasmatic nuclei (SCN), the pacemaking circadian brain locus, despite other claims that SCN neurons were somehow exceptional to these imprinting rules. In addition, Ube3a-deficient mice lack the typical drop in wake late in the dark period and have blunted responses to sleep deprivation. Suppression of physical activity by light in Ube3a-deficient mice is not due to anxiety as measured by behavioral tests and stress hormones; quantification of stress hormones may provide a mechanistic link to sleep alteration and memory deficits caused by Ube3a deficiency, and serve as an easily measurable biomarker for evaluating potential therapeutic treatments for Angelman syndrome. We conclude that reduced Ube3a gene dosage affects not only neurodevelopment but also sleep patterns and circadian rhythms.

12.
JACS Au ; 1(9): 1497-1505, 2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34604858

RESUMEN

Covalent organic frameworks (COFs) are an emerging type of porous crystalline material for efficient catalysis of the oxygen evolution reaction (OER). However, it remains a grand challenge to address the best candidates from thousands of possible COFs. Here, we report a methodology for the design of the best candidate screened from 100 virtual M-N x O y (M = 3d transition metal)-based model catalysts via density functional theory (DFT) and machine learning (ML). The intrinsic descriptors of OER activity of M-N x O y were addressed by the machine learning and used for predicting the best structure with OER performances. One of the predicted structures with a Ni-N2O2 unit is subsequently employed to synthesize the corresponding Ni-COF. X-ray absorption spectra characterizations, including XANES and EXAFS, validate the successful synthesis of the Ni-N2O2 coordination environment. The studies of electrocatalytic activities confirm that Ni-COF is comparable with the best reported COF-based OER catalysts. The current density reaches 10 mA cm-2 at a low overpotential of 335 mV. Furthermore, Ni-COF is stable for over 65 h during electrochemical testing. This work provides an accelerating strategy for the design of new porous crystalline-material-based electrocatalysts.

13.
Am J Transl Res ; 13(8): 9715-9721, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34540100

RESUMEN

OBJECTIVE: This study explored and analyzed the effects of bilateral and unilateral early sucking within 2 h after delivery on lactation. METHODS: From August 2019 to August 2020, 392 primiparas with full-term, singleton, natural delivery, and normal breast conditions were submitted to the Obstetrics Department of our hospital and were enrolled as the research subjects. The subjects were randomly divided into an experimental group and a control group, with 196 in each group. Both groups implemented early sucking with the assistance of a midwife within 2 h after delivery. The experimental group conducted bilateral breast sucking and the control group received unilateral sucking. The onset time of colostrum, the lactation volume, and the prolactin levels at 6 h, 24 h, 48 h, and 72 h after delivery, including neonatal urination and incidence of complications were compared between the two groups. RESULTS: The onset time of colostrum in the experimental group was much earlier than that in the control group with a statistically significant difference (P<0.05). The postpartum filling time of the experimental group was shorter than that of the control group, with a statistically significant difference (P<0.05). There was a statistically insignificant difference in the distribution of lactation yield between the two groups at 6 h of postpartum (P>0.05). The lactation yield distribution in the experimental group at 24 h, 48 h, and 72 h was critically superior to that in control group, with statistically significant difference (P<0.05). The degree of prolactin in the experimental group was higher than that in the control group (P<0.05). There was no significant difference in urination frequency and the incidence of complications between the two groups of neonates at 24 h, 48 h, and 72 h (P>0.05). CONCLUSION: The effect of bilateral early lactation within 2 h after delivery is superior to that of unilateral early lactation, which is worthy of clinical application.

14.
Chemistry ; 27(58): 14390-14395, 2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34383348

RESUMEN

Imines are important intermediates in drug synthesis. Photocatalytic aerobic oxidative coupling of amines has been considered as a clean and promising way to produce imines and has attracted great attention. Herein, we designed and synthesized a novel two-dimensional porphyrin-based covalent organic framework (Por-BC-COF) which adopts an AA stacking mode with excellent crystallinity, high Brunauer-Emmett-Teller surface areas (1200 m2 g-1 ), wide light absorption range (200-1300 nm) and good stability in a variety of organic solvents. Por-BC-COF can be used as a metal-free heterogeneous photocatalyst for the photocatalytic oxidation of amines to imines under visible light and red light with a high yield (97 %). This work presents a novel and efficient COF photocatalyst in the application of light-driven organic synthesis.

15.
Anesthesiology ; 135(1): 122-135, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33951177

RESUMEN

BACKGROUND: Isoflurane can induce anterograde amnesia. Hippocampal ripples are high-frequency oscillatory events occurring in the local field potentials of cornu ammonis 1 involved in memory processes. The authors hypothesized that isoflurane suppresses hippocampal ripples at a subanesthetic concentration by modulating the excitability of cornu ammonis 1 neurons. METHODS: The potencies of isoflurane for memory impairment and anesthesia were measured in mice. Hippocampal ripples were measured by placing recording electrodes in the cornu ammonis 1. Effects of isoflurane on the excitability of hippocampal pyramidal neurons and interneurons were measured. A simulation model of ripples based on the firing frequency of hippocampal cornu ammonis 1 neurons was used to validate the effects of isoflurane on neuronal excitability in vitro and on ripples in vivo. RESULTS: Isoflurane at 0.5%, which did not induce loss of righting reflex, impaired hippocampus-dependent fear memory by 97.4 ± 3.1% (mean ± SD; n = 14; P < 0.001). Isoflurane at 0.5% reduced ripple amplitude (38 ± 13 vs. 42 ± 13 µV; n = 9; P = 0.003), rate (462 ± 66 vs. 538 ± 81 spikes/min; n = 9; P = 0.002) and duration (36 ± 5 vs. 48 ± 9 ms; n = 9; P < 0.001) and increased the interarrival time (78 ± 7 vs. 69 ± 6 ms; n = 9; P < 0.001) and frequency (148.2 ± 3.9 vs. 145.0 ± 2.9 Hz; n = 9; P = 0.001). Isoflurane at the same concentration depressed action potential frequency in fast-spiking interneurons while slightly enhancing action potential frequency in cornu ammonis 1 pyramidal neurons. The simulated effects of isoflurane on hippocampal ripples were comparable to recordings in vivo. CONCLUSIONS: The authors' results suggest that a subanesthetic concentration of isoflurane can suppress hippocampal ripples by differentially modulating the excitability of pyramidal neurons and interneurons, which may contribute to its amnestic action.


Asunto(s)
Anestésicos por Inhalación/farmacología , Hipocampo/efectos de los fármacos , Interneuronas/efectos de los fármacos , Isoflurano/farmacología , Células Piramidales/efectos de los fármacos , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales
16.
Prog Neurobiol ; 202: 102041, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33766679

RESUMEN

Neuropathic pain affects up to 10 % of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA. Accordingly, pain-related symptoms were significantly alleviated by NALCN-siRNA-mediated NALCN knockdown and completely prevented by NALCN-shRNA-mediated NALCN knockdown in rats or by conditional NALCN knockout in mice. Our results indicate that increases in NALCN expression and function contribute to CCI-induced neuronal sensitization; therefore, NALCN may be a novel molecular target for control of neuropathic pain.


Asunto(s)
Neuralgia , Canales de Sodio , Animales , Ganglios Espinales , Hiperalgesia , Ratones , Neuronas , ARN Interferente Pequeño , Ratas , Sodio
17.
Ann Transl Med ; 8(21): 1397, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33313142

RESUMEN

BACKGROUND: Preliminary observation in clinical practice showed that subjective neurocognitive complaints are relatively common in bullous pemphigoid (BP) patients. Yet, little has been done to investigate the neurocognitive status in BP. METHODS: This is a multicenter observational case-control study comprised of 61 BP patients and 65 matched control subjects from 3 medical centers in China from 2014 to 2019. To evaluate the cognitive function between BP patients and matched controls, all the subjects finished the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA). RESULTS: The overall scores were significantly lower in BP than in controls (PMoCA<0.001). The percentage of patients screened positive for cognitive impairment in the BP group was significantly higher than in the control group (PMMSE<0.001, PMoCA<0.001). On multivariate analysis, BP was associated with increased odds of cognitive impairment by MMSE and MoCA (PMMSE=0.017, PMoCA=0.007). CONCLUSIONS: BP patients had decreased cognitive abilities and were at a higher risk of cognitive impairment. The evaluation of cognitive impairment may be warranted for BP patients in clinical practice for early diagnosis and therapy of dementia.

18.
Anesthesiology ; 133(4): 824-838, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32773689

RESUMEN

BACKGROUND: Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. METHODS: The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. RESULTS: Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel-mediated holding currents and conductance from -75.0 ± 12.9 to -130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel-mediated holding conductance. CONCLUSIONS: Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.


Asunto(s)
Anestésicos por Inhalación/administración & dosificación , Canales Iónicos/agonistas , Proteínas de la Membrana/agonistas , Neuronas/efectos de los fármacos , Respiración/efectos de los fármacos , Complejo Olivar Superior/efectos de los fármacos , Animales , Femenino , Canales Iónicos/fisiología , Masculino , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Técnicas de Cultivo de Órganos , Canales de Sodio/fisiología , Complejo Olivar Superior/fisiología
19.
Front Immunol ; 11: 1607, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32793235

RESUMEN

Objectives: The clinical outcome of bullous pemphigoid appears worse in patients with infectious complications, and assessment of the prevalence and risk factors of infectious complications could be necessary to plan preventative strategies and to instruct the treatment plans. We sought to determine the risk factors of infection and compare associated factors in inpatients and outpatients with different system infections. Design: This is a single-centered retrospective study on the medical records of 252 patients from 2010 to 2018 at the dermatology department, Peking Union Medical College. Medical profiles of medical history, diagnosis, infectious complications, and treatment plans were analyzed. The associated factors were compared between the subgroups, including inpatients and outpatients, different body sites of infection. Results: Of the total 252 patients with bullous pemphigoid (BP), 81 patients (81/252, 32.1%) had infectious complications. Forty-eight patients died from pulmonary infections (11/48, 22.9%), cardiovascular diseases (6/48, 12.5%), and other diseases. Infections were most frequently found in skin/mucosa (44/252, 17.5%), respiratory system (32/252, 12.7%), and blood (10/252, 4.0%). On multivariate analysis, risk factors of infections in BP were maximal control dose of corticosteroids (OR 2.539, 95% CI 1.456-4.430, p = 0.001), low serum albumin level (OR 2.557, 95% CI 1.283, 5.092, p = 0.007), hospitalization (OR 4.025, 95% CI 2.289, 7.079, p < 0.001), comorbidities including respiratory disease (OR 4.060, 95% CI, 1.861, 8.858, p < 0.001), eye disease (OR 4.431, 95% CI 1.864, 10.532, p < 0.001), and diabetes (OR 2.667, 95% CI 1.437, 4.949, p = 0.002). The rate of infection was significantly higher in inpatients compared to that in outpatients (54.0 vs. 20.6%, p < 0.001), with diverse risk factors. Mucocutaneous infections were associated with a maximal control dose of corticosteroid and other dermatoses. Respiratory infections were related to respiratory disease and old age, and hematologic infection was associated with low serum hemoglobin levels and mucosal involvement of BP. Both of them were associated with mucosal involvement of BP and high titer anti-BP180 antibody. Conclusions: Infectious complications of bullous pemphigoid are common and are associated with mucosal involvement of BP, more comorbidities, the higher dose of corticosteroids, and the lower level of serum albumin.


Asunto(s)
Infecciones/etiología , Penfigoide Ampolloso/complicaciones , Corticoesteroides/uso terapéutico , Anciano , Femenino , Humanos , Infecciones/diagnóstico , Infecciones/tratamiento farmacológico , Infecciones/microbiología , Pacientes Internos , Masculino , Pacientes Ambulatorios , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/metabolismo
20.
Ther Adv Chronic Dis ; 11: 2040622320916023, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32426100

RESUMEN

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease characterized by suprabasal acantholysis, causing painful mucocutaneous blisters and erosions. Current mainstay therapy for pemphigus is systemic corticosteroids in combination with or without immunosuppressive adjuvants, which may cause severe adverse effects and seriously impact on the quality of life in pemphigus patients. The objective of this study was to evaluate the efficacy and safety of thalidomide therapy in patients with PV. METHODS: This study examined six PV patients from June 5, 2017, to November 11, 2018, in the dermatology department of Peking Union Medical College Hospital. Treatment with thalidomide was applied at a dose of 50-100 mg/day for disease control. RESULTS: The mean age of the six patients (two male and four female patients) at the time of thalidomide therapy initiation was 50.2 years (range: 38-67 years), and the total duration of follow-up after thalidomide therapy was 13.2 months (range: 5-25 months). All patients responded favorably to thalidomide treatment, and three patients showed a dramatic reduction in anti-Dsg3 autoantibodies in the serologic examinations within 1 year. Five patients were found to have mucosal involvement. Mild adverse effects were noted in three patients, which could be managed after the application of symptomatic treatment and did not interfere with the pemphigus therapy. CONCLUSION: These results demonstrate that thalidomide could be an effective and safe option for PV patients, especially those who are concerned about steroid-induced severe complications, and have mucosal diseases.

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