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1.
Immunity ; 56(2): 320-335.e9, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36693372

RESUMEN

Neuronal signals have emerged as pivotal regulators of group 2 innate lymphoid cells (ILC2s) that regulate tissue homeostasis and allergic inflammation. The molecular pathways underlying the neuronal regulation of ILC2 responses in lungs remain to be fully elucidated. Here, we found that the abundance of neurotransmitter dopamine was negatively correlated with circulating ILC2 numbers and positively associated with pulmonary function in humans. Dopamine potently suppressed lung ILC2 responses in a DRD1-receptor-dependent manner. Genetic deletion of Drd1 or local ablation of dopaminergic neurons augmented ILC2 responses and allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired the mitochondrial oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effect of dopamine. Local administration of dopamine alleviated allergen-induced ILC2 responses and airway inflammation. These findings demonstrate that dopamine represents an inhibitory regulator of ILC2 responses in allergic airway inflammation.


Asunto(s)
Inmunidad Innata , Neumonía , Humanos , Dopamina/metabolismo , Linfocitos , Pulmón/metabolismo , Neumonía/metabolismo , Inflamación/metabolismo , Interleucina-33/metabolismo
3.
J Hepatol ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39094743

RESUMEN

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96. METHODS: In this multicentre randomized controlled clinical trial, 180 non-cirrhotic HBeAg-negative chronic hepatitis B patients on continuous NUC therapy for ≥ 2.5 years with HBV DNA levels < 60 IU/mL were randomized to discontinue NUC (n=90) or receive 48 weeks of PegIFN-α-2a treatment (n=90) and followed up till 96 weeks. The primary endpoint was the virological relapse rate until week 96. RESULTS: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, P < 0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, P = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, P = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, P = 0.03) than the NUC cessation group. CONCLUSIONS: Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and achieves higher HBsAg loss rates than NUC treatment cessation alone in HBeAg-negative chronic hepatitis B patients. IMPACT AND IMPLICATIONS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimised scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96 in HBeAg-negative chronic hepatitis B patients. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, P < 0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, P= 0.03) than the NUC cessation group until week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER: NCT02594293.

4.
Mol Psychiatry ; 28(2): 767-779, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36203006

RESUMEN

Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1ß. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.


Asunto(s)
Analgésicos Opioides , Hiperalgesia , Animales , Femenino , Masculino , Ratones , Astrocitos/metabolismo , Gliosis , Hiperalgesia/inducido químicamente , Hiperalgesia/genética , Hiperalgesia/metabolismo , Morfina , Dolor , Vía de Señalización Wnt
5.
Mol Psychiatry ; 28(9): 3955-3965, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37798418

RESUMEN

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.


Asunto(s)
Ansiolíticos , Metformina , Humanos , Ratones , Animales , Ansiolíticos/farmacología , Proteínas Quinasas Activadas por AMP/farmacología , Metformina/farmacología , Hipoglucemiantes/farmacología , Corteza Prefrontal , Neuronas GABAérgicas
6.
Acta Pharmacol Sin ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39349767

RESUMEN

Depressive disorders are a global mental health challenge that is closely linked to inflammation, especially in the post-COVID-19 era. The JAK-STAT pathway, which is primarily associated with inflammatory responses, is not fully characterized in the context of depressive disorders. Recently, a phase 3 retrospective cohort analysis heightened that the marketed JAK inhibitor tofacitinib is beyond immune diseases and has potential for preventing mood disorders. Inspired by these clinical facts, we investigated the role of the JAK-STAT signaling pathway in depression and comprehensively assessed the antidepressant effect of tofacitinib. We found that aberrant activation of the JAK-STAT pathway is highly conserved in the hippocampus of classical depressive mouse models: LPS-induced and chronic social defeat stress (CSDS)-induced depressive mice. Mechanistically, the JAK-STAT pathway mediates proinflammatory cytokine production and microgliosis, leading to synaptic defects in the hippocampus of both depressive models. Remarkably, the JAK inhibitor tofacitinib effectively reverses these phenomena, contributing to its antidepressant effect. These findings indicate that the JAK/STAT pathway could be implicated in depressive disorders, and suggest that the JAK inhibitor tofacitinib has a potential translational implication for preventing mood disorders far beyond its current indications.

7.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-39319473

RESUMEN

OBJECTIVES: To summarize the best evidence for the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy. METHODS: Evidence related to the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy, including practice guidelines, systematic evaluation, expert consensuws and evidence summary was systematically searched in UpToDate, BMJ Best Practice, World Health Organization (WHO) website, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE) website, National Guidelines website, American Society for Reproductive Medicine (ASRM) website, New York Academy of Sciences (NYAS) website, Joanna Briggs Institute (JBI) database, Cochrane Library, CINAHL, PubMed, Wanfang Knowledge Data Service Platform, CNKI, and China Biomedical Literature Database from inception to March 1, 2024. Two researchers independently evaluated the quality of the literature, and a senior researcher made the final decision for literature inclusion. RESULTS: A total of 14 articles met the criteria, including 5 practical guidelines, 3 systematic evaluations, 2 expert consensuses, 1 evidence summary paper and 3 from UptoDate. The final formation includes five aspects: risk assessment, disease monitoring, early prevention, institutional management, and health education, with a total of 27 best pieces of evidence. CONCLUSIONS: The updated evidence indicates that the monitoring and prevention of ovarian hyperstimulation syndrome should start early; medical practitioners should provide personalized treatment plans for patients, promote the rational allocation of treatment resources, and enhance effective management of ovarian hyperstimulation syndrome.

8.
BMC Genomics ; 24(1): 332, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37322453

RESUMEN

The rich genetic diversity in Citrullus lanatus and the other six species in the Citrullus genus provides important sources in watermelon breeding. Here, we present the Citrullus genus pan-genome based on the 400 Citrullus genus resequencing data, showing that 477 Mb contigs and 6249 protein-coding genes were absent in the Citrullus lanatus reference genome. In the Citrullus genus pan-genome, there are a total of 8795 (30.5%) genes that exhibit presence/absence variations (PAVs). Presence/absence variation (PAV) analysis showed that a lot of gene PAV were selected during the domestication and improvement, such as 53 favorable genes and 40 unfavorable genes were identified during the C. mucosospermus to C. lanatus landrace domestication. We also identified 661 resistance gene analogs (RGAs) in the Citrullus genus pan-genome, which contains 90 RGAs (89 variable and 1 core gene) located on the pangenome additional contigs. By gene PAV-based GWAS, 8 gene presence/absence variations were found associated with flesh color. Finally, based on the results of gene PAV selection analysis between watermelon populations with different fruit colors, we identified four non-reference candidate genes associated with carotenoid accumulation, which had a significantly higher frequency in the white flesh. These results will provide an important source for watermelon breeding.


Asunto(s)
Citrullus , Citrullus/genética , Domesticación , Fitomejoramiento , Genoma de Planta , Análisis de Secuencia de ADN
9.
J Med Virol ; 95(2): e28550, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36734068

RESUMEN

Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has received much attention since it is associated with mortality and is hypothesized as the cause of long COVID-19 and the emergence of a new variant of concerns. However, a prediction model for the accurate prediction of prolonged infection is still lacking. A total of 2938 confirmed patients with COVID-19 diagnosed by positive reverse transcriptase-polymerase chain reaction tests were recruited retrospectively. This study cohort was divided into a training set (70% of study patients; n = 2058) and a validation set (30% of study patients; n = 880). Univariate and multivariate logistic regression analyses were utilized to identify predictors for prolonged infection. Model 1 included only preadmission variables, whereas Model 2 also included after-admission variables. Nomograms based on variables of Model 1 and Model 2 were built for clinical use. The efficiency of nomograms was evaluated by using the area under the curve, calibration curves, and concordance indexes (C-index). Independent predictors of prolonged infection included in Model 1 were: age ≥75 years, chronic kidney disease, chronic lung disease, partially or fully vaccinated, and booster. Additional independent predictors in Model 2 were: treated with nirmatrelvir/ritonavir more than 5 days after diagnosis and glucocorticoid. The inclusion of after-admission variables in the model slightly improved the discriminatory power (C-index in the training cohort: 0.721 for Model 1 and 0.737 for Model 2; in the validation cohort: 0.699 for Model 1 and 0.719 for Model 2). In our study, we developed and validated predictive models based on readily available variables of preadmission and after-admission for predicting prolonged SARS-CoV-2 infection of patients with COVID-19.


Asunto(s)
COVID-19 , Humanos , Anciano , Nomogramas , SARS-CoV-2 , Estudios Retrospectivos , Síndrome Post Agudo de COVID-19
10.
J Med Virol ; 95(8): e28997, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37537950

RESUMEN

During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection.


Asunto(s)
COVID-19 , Faringitis , Femenino , Humanos , China/epidemiología , Estudios de Cohortes , Tos , COVID-19/epidemiología , Fatiga , Fiebre , Incidencia , Dolor , Reinfección/epidemiología , SARS-CoV-2 , Masculino
11.
Brain Behav Immun ; 112: 96-117, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37286175

RESUMEN

Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses.


Asunto(s)
Colitis , Inmunidad Innata , Receptores Inmunológicos , Receptor Activador Expresado en Células Mieloides 1 , Humanos , Colitis/inmunología , Colitis/patología , Colitis/psicología , Giro del Cíngulo , Inflamación , Microglía/metabolismo , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Animales , Ratones , Receptores Inmunológicos/metabolismo
12.
BMC Infect Dis ; 23(1): 698, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853317

RESUMEN

INTRODUCTION: The SARS-CoV-2 Omicron variant has decreased virulence and pathogenicity, yet the number of Omicron infections worldwide is unprecedentedly high, with rather high mortality and severe disease rate. Chronic kidney disease (CKD) patients are particularly vulnerable to the SARS-CoV-2 Omicron variant and have unique clinical outcomes. METHODS: We retrospectively collected data from 2140 hospitalized patients with SARS-CoV-2 Omicron variant infection from March 29, 2022, to May 17, 2022. Demographic characteristics, ancillary examination results, and clinical treatments were described. Occurrence of critical COVID-19 or death and time of positive-to-negative conversion was defined as primary outcomes. The presence of COVID-19 pneumonia and the usage of respiratory or circulatory support was defined as secondary outcomes. Univariate or multivariate logistic regression analyses were performed to identify risk factors for primary outcomes. RESULTS: 15.74% of CKD patients infected with the SARS-CoV-2 Omicron variant ended up with critical COVID-19 or death. Pre-existing CKD was a risk factor for critical COVID-19 or death and prolonged time of positive-to-negative conversion of SARS-CoV-2. Nirmatrelvir-ritonavir facilitated viral clearance among COVID-19 patients with non-severe CKD. CONCLUSION: We found patients with CKD and COVID-19 due to Omicron experienced worse clinical outcomes and prolonged time of positive-to-negative conversion of SARS-CoV-2 compared to patients without CKD, which helps rationalize limited medical resources and offers guidance for appropriate clinical treatments.


Asunto(s)
COVID-19 , Insuficiencia Renal Crónica , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Factores de Riesgo , Hospitales , Insuficiencia Renal Crónica/complicaciones
13.
Phys Chem Chem Phys ; 25(7): 5694-5700, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36734480

RESUMEN

Borophene has been reported as the latest very promising 2D material. We theoretically investigate the thermal radiation of ß12 borophene. ß12 borophene has been composited on Ag substrate. Theoretical research frequently mentions three types of model of ß12 borophene. The energy bands of the three models are different. Homogeneous and inversion symmetric models have a gapless Dirac cone near the K(K') point, while they are gapped in the inversion non-symmetric model. The homogeneous model has gapless triplet fermions and three-band touching points at high-symmetry points. The optical conductivity exhibits peaks due to the energy transition of high-symmetry points. The radiation spectrum follows Wien's displacement law in homogeneous and inversion symmetric models, while it is broken in the inversion non-symmetric model. The total energy radiation changes as the voltage increases for the three ß12 borophene models. The radiation of energy can be controlled by applying a suitable voltage.

14.
Arch Insect Biochem Physiol ; 114(2): 1-14, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37032456

RESUMEN

Ischnura senegalensis Rambur, 1842 is among the most widespread damselfly species in the world. Unlike dragonflies with strong migration abilities, I. senegalensis have limited dispersing abilities. Gene flow among I. senegalensis populations may be greatly influenced by anthropogenic disturbance, fragmented suitable habitats, sea straits, or even global warming. In this study, to investigate the genetic diversity of I. senegalensis populations, we sequenced and collected 498 cytochrome oxidase I sequences across the Old World. Haplotype network analysis showed 51 haplotypes and I. senegalensis could be grouped into four regions (Afrotropical region, Oriental region, main Islands of Japan, and the Ryukyu Islands), each of which contains different dominant haplotypes. Based on molecular variance analysis, we found that populations from the Afrotropical region have quite a low gene flow with the Asian populations (except Yemen). Furthermore, rice cultivation may aid the dispersion of I. senegalensis in the oriental region. Populations from the Ryukyu Islands show the highest genetic diversity, which may be due to the geological separation among islands. Our results prove that I. senegalensis has great genetic diversity among different populations across the world.


Asunto(s)
Genética de Población , Odonata , Animales , Variación Genética , Odonata/genética , Haplotipos , Flujo Génico , Filogenia
15.
J Environ Manage ; 336: 117686, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36967692

RESUMEN

Dosing zero valent iron (ZVI) or sodium hydroxide (NaOH) is the common method of addressing acidification in anaerobic digestion (AD) systems; however, few studies have discussed and compared their effects on microbial metabolism. In the present study, microbial syntrophy and metabolic pathways under ZVI and NaOH regulation are comparatively analyzed through microbial network analysis and metagenomic/metaproteomic analyses. CH4 yield in the ZVI reactor was 414 mL/gVS, an increase of 23% when compared with that in the reactor with NaOH dosing (336 mL/gVS). The methanogenesis recovery period in the ZVI reactor (37 days) was shorter than that in the NaOH reactor (48 days). Co-occurrence networks indicated that ZVI promoted Methanoculleus and Methanosarcina to establish a complex syntrophic association with SAO bacteria (Syntrophaceticus and Aminobacterium) and syntrophic acetogens (Syntrophomonas), strengthening SAO-hydrogenotrophic methanogenesis (HM) and acetoclastic methanogenesis (AM) pathways simultaneously. Metagenomic analysis showed that the relative abundance of mcrA and fwdB in the ZVI reactor was higher 27% than that in the NaOH reactor. Furthermore, through metaproteomics analysis, much more enzymes related to glucose degradation, bioconversion of butyric acid and pyruvate, conversion of formate and acetate to CO2, and production of CH4 from acetate and CO2 were significantly upregulated under ZVI regulation than under NaOH regulation (fold change relative to control [FC] > 1.5, p < 0.05). The results of the present study enhance our understanding of methanogenic mechanisms under the regulation of ZVI, providing a theoretical basis for its practical application in AD systems experiencing VFA suppression.


Asunto(s)
Dióxido de Carbono , Hierro , Anaerobiosis , Hidróxido de Sodio , Bacterias Anaerobias/metabolismo , Metano , Reactores Biológicos/microbiología
16.
J Tissue Viability ; 32(4): 590-595, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37563057

RESUMEN

BACKGROUND: Pressure injuries (PIs) continue to present significant challenges. In recent years, the number of patients with present-on-admission pressure injury (POA-PI) has increased, but researchers have devoted little attention to it, and little is known about its clinical outcome. AIMS: To compare the clinical outcomes of POA-PI and hospital-acquired pressure injury (HAPI) patients. METHODS: In this study, hospitalized patients with pressure injuries were divided into two groups based on whether they acquired the injury in the hospital or already present at the time of their admission. The disease prognosis, duration of stay, and healthcare costs of patients with HAPI and POA-PI were evaluated using propensity score matching analysis (PSM), t-tests, and Mann-Whitney U tests. RESULTS: The information on 1871 patients was retrieved from the electronic case system retroactively. A total of 305 pairs of patients were effectively matched between the two groups using propensity score matching (HAPI group = 305, POA-PI group = 305). There was no statistically significant difference at characteristics between the two groups (P > 0.05). The percentage of POA-PI group patients who were discharged from the hospital was greater than that of the HAPI group (P < 0.05). Conversely, the percentage of POA-PI group patients who died, ceased receiving treatment, or transferred to the hospital was lower than that of the HAPI group. Patients in the POA-PI group had shorter hospital stays than those in the HAPI group (P < 0.05). Patients in the POA-PI group had lower healthcare costs than those in the HAPI group (P < 0.05). CONCLUSIONS: Patients with POA-PI have superior clinical outcomes than patients with HAPI, but make up the overwhelming majority of hospitalized patients. It is imperative that future research focuses on the reduction of POA-PI and HAPI incidence and the identification of therapies that will enhance patient prevention for these conditions.


Asunto(s)
Úlcera por Presión , Humanos , Úlcera por Presión/prevención & control , Puntaje de Propensión , Hospitalización , Tiempo de Internación , Hospitales
17.
Plant Foods Hum Nutr ; 78(1): 68-75, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36322321

RESUMEN

Lycium barbarum (LB) is a famous traditional Chinese medicinal plant as well as food supplement possessing various pharmacological functions such as anti-aging and antioxidant effects. The Parkinson's disease (PD)-related kinase Pink1 plays vital role in maintaining the neuron cell homeostasis, having been recognized as a potential target for the development of anti-PD drugs. In this work, the neuroprotective effects of methanol extract of LB fruit (LBFE) were investigated using a Drosophila PD model (PINK1B9) and a human neuroblastoma SH-SY5Y cell line. We found that when LBFE was supplied to the PINK1B9 flies at 6, 12, and 18 days of age, it raised the ATP and dopamine levels at all ages, extended life span, improved motor behavior, and rescued olfactory deficits of the PINK1B9 flies. In addition, histopathological examinations indicated that muscle atrophy in thoraces of the mutant flies was significantly repaired. Finally, LBFE was able to rescue the SH-SY5Y cells against MPP+-induced neurotoxicity. This work reports for the first time the anti-PD potential of L. barbarum fruit extract in PINK1 mutant fruit flies, presenting a new viewpoint for studing the mechanism of action of LBFE.


Asunto(s)
Proteínas de Drosophila , Lycium , Neuroblastoma , Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , Humanos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Enfermedad de Parkinson/genética , Fármacos Neuroprotectores/farmacología , Lycium/metabolismo , Modelos Genéticos , Extractos Vegetales/farmacología , Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/farmacología , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/farmacología
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(6): 1011-1014, 2023 Dec 30.
Artículo en Zh | MEDLINE | ID: mdl-38173115

RESUMEN

One case with ascites and lower limb edema as the initial manifestations was reported.The echocardiography revealed inferior vena cava and right atrial occupation,which combined with increased alpha fetoprotein and imaging examination,suggested liver malignant tumor combined with tumor thrombus of inferior vena cava and right atrium.After targeted therapy combined with immunotherapy,the tumor shrank and alpha fetoprotein decreased significantly,suggesting that the treatment was effective.The median survival time of the patient was 3 months.This patient had a clear history of cirrhosis due to hepatitis B and was clinically diagnosed with advanced liver cancer,which suggested the importance of early liver cancer screening.


Asunto(s)
Neoplasias Hepáticas , Vena Cava Inferior , Humanos , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología , alfa-Fetoproteínas , Ecocardiografía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Neoplasias Hepáticas/patología
19.
J Viral Hepat ; 29(6): 412-419, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35293082

RESUMEN

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10 years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR = 9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4 levels (OR = 0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4 may be a protective factor for thyroid dysfunction.


Asunto(s)
Hepatitis B Crónica , Hipotiroidismo , Enfermedades de la Tiroides , China/epidemiología , Estudios de Seguimiento , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/tratamiento farmacológico , Incidencia , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Factores de Riesgo , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/epidemiología , Tirotropina
20.
Acta Pharmacol Sin ; 43(7): 1699-1709, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34811511

RESUMEN

Hypidone hydrochloride (YL-0919) is a novel antidepressant in clinical phase II trial. Previous studies show that YL-0919 is a selective 5-HT (serotonin) reuptake inhibitor, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist, which exerts antidepressant effects in various animal models, but its effects on neural function remain unclear. Medial prefrontal cortex (mPFC), a highly evolved brain region, controls highest order cognitive functions and emotion regulation. In this study we investigated the effects of YL-0919 on the mPFC function, including the changes in neuronal activities using electrophysiological recordings. Extracellular recording (in vivo) showed that chronic administration of YL-0919 significantly increased the spontaneous discharges of mPFC neurons. In mouse mPFC slices, whole-cell recording revealed that perfusion of YL-0919 significantly increased the frequency of sEPSCs, but decreased the frequency of sIPSCs. Then we conducted whole-cell recording in mPFC slices of GAD67-GFP transgenic mice, and demonstrated that YL-0919 significantly inhibited the excitability of GABAergic neurons. In contrast, it did not alter the excitability of pyramidal neurons in mPFC slices of normal mice. Moreover, the inhibition of GABAergic neurons by YL-0919 was prevented by pre-treatment with 5-HT1A receptor antagonist WAY 100635. Finally, chronic administration of YL-0919 significantly increased the phosphorylation levels of mTOR and GSK-3ß in the mPFC as compared with vehicle. Taken together, our results demonstrate that YL-0919 enhances the excitability of mPFC via a disinhibition mechanism to fulfill its rapid antidepressant neural mechanism, which was accomplished by 5-HT1A receptor-mediated inhibition of inhibitory GABAergic interneurons.


Asunto(s)
Antidepresivos , Receptor de Serotonina 5-HT1A , Animales , Antidepresivos/farmacología , Neuronas GABAérgicas , Glucógeno Sintasa Quinasa 3 beta , Ratones , Piperidinas , Corteza Prefrontal , Piridonas , Antagonistas de la Serotonina , Agonistas de Receptores de Serotonina , Inhibidores Selectivos de la Recaptación de Serotonina
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