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1.
Crit Care ; 24(1): 219, 2020 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-32410714

RESUMEN

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Cuidados Críticos , Brotes de Enfermedades , Unidades de Cuidados Intensivos , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Anciano , COVID-19 , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , Resultado del Tratamiento
2.
J Cell Physiol ; 234(10): 18906-18916, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30953350

RESUMEN

Bone marrow mesenchymal stem cells (BMSC) can ameliorate ischemic injury of various tissues. However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC-derived conditioned medium (BMSC-CM) on hypoxia/reoxygenation (H/R)-induced injury of H9c2 myocardial cells, and the potential mechanisms. Cell injury was determined through level of cell viability, lactate dehydrogenase (LDH) release, total intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), and cell apoptosis. Autophagic activity of cells was detected through levels of the autophagy-associated proteins and autophagic flux. Results showed that BMSC-CM alleviated H/R-induced injury in H9c2 cells, as demonstrated by increased cell viability and Δψm, decreased ROS production, LDH release, and cell apoptosis. Furthermore, the H/R treatment induced a decrease in autophagic activity and an increase in Notch2 signaling activation in H9c2 cells. In the presence of BMSC-CM, the autophagic activity impaired by the H/R treatment was upregulated with decreased phosphorylation of mTOR, and the activation of Notch2 signaling was downregulated. These effects of BMSC-CM could be replicated by Notch signaling inhibitor. In contrast, inhibitors of cell autophagy including chloroquine (CQ) and 3-methyladenine, diminished the protective effects of BMSC-CM. Taken together results, our study showed that BMSC-CM could protect H9c2 cells from H/R-induced injury potentially through regulating Notch2/mTOR/autophagy signaling. These findings may provide a novel insight into the mechanisms of BMSC-CM in therapy of myocardial ischemia/reperfusion injury as well as other ischemic diseases.


Asunto(s)
Autofagia/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Células Madre Mesenquimatosas/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Receptor Notch2/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/fisiología , Autofagia/fisiología , Células de la Médula Ósea/metabolismo , Hipoxia de la Célula/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología
3.
Stroke ; 48(6): 1646-1654, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28487326

RESUMEN

BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked ß-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke. METHODS: Mice with Xbp1 loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation. RESULTS: Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice. CONCLUSIONS: Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.


Asunto(s)
Acetilglucosamina/metabolismo , Isquemia Encefálica/metabolismo , Proteínas de la Membrana/metabolismo , Neuroprotección/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Piranos/farmacología , Accidente Cerebrovascular/metabolismo , Tiazoles/farmacología , Respuesta de Proteína Desplegada/fisiología , Proteína 1 de Unión a la X-Box/metabolismo , Factores de Edad , Animales , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Pliegue de Proteína
4.
iScience ; 27(3): 109165, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38420589

RESUMEN

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality, and its severity is closely related to the short-term prognosis of SAH patients. S100 calcium-binding protein A9 (S100A9) has been shown to be associated with some neurological diseases. In this study, the concentration of S100A9 in clinical cerebrospinal fluid samples was detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between S100A9 and the prognosis of patients was explored. In addition, WT mice and S100A9 knockout mice were used to establish an in vivo SAH model. Neurological scores, brain water content, and histopathological staining were performed after a specified time. A co-culture model of BV2 and HT22 cells was treated with heme chloride to establish an in vitro SAH model. Our study confirmed that the expression of S100A9 protein in the CSF of SAH patients is increased, and it is related to the short-term prognosis of SAH patients. S100A9 protein is highly expressed in microglia in the central nervous system. S100A9 gene knockout significantly improved neurological function scores and reduced neuronal apoptosis. S100A9 protein can activate TLR4 receptor, promote nuclear transcription of NF-κB, increase the activation of inflammatory body, and ultimately aggravate nerve injury.

5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(1): 43-50, 2023 Jan.
Artículo en Zh | MEDLINE | ID: mdl-36880237

RESUMEN

OBJECTIVE: To investigate and compare the regulatory effects of umbilical cord mesenchymal stem cells (MSC) and their conditioned medium (MSC-CM) on gut microbiota of septic mice. METHODS: Twenty-eight six-to-eight-week-old female C57BL/6J mice were randomly divided into sham operation group (Sham group), sepsis model group (CLP group), sepsis+MSC treatment group (CLP+MSC group) and sepsis+MSC-CM treatment group (CLP+MSC-CM group), with seven mice in each group. The septic mouse model was established by cecal ligation and puncture (CLP). In Sham group, CLP were not performed, and other operations were the same as CLP group. Mice in the CLP+MSC group and CLP+MSC-CM group received 0.2 mL 1×106 MSC or 0.2 mL concentrated MSC-CM via intraperitoneal injection 6 hours after CLP, respectively. Sham group and CLP group were given 0.2 mL sterile phosphate buffer saline (PBS) via intraperitoneal injection. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and colon length. Levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assay (ELISA). Phenotype of peritoneal macrophages was analyzed by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. RESULTS: Compared with Sham group, significant inflammatory injury in lung and colon was observed, and shorter colon was detected in CLP group (cm: 6.00±0.26 vs. 7.11±0.09), the level of inflammatory cytokine interleukin-1ß (IL-1ß) in serum was significantly increased (ng/L: 432.70±17.68 vs. 353.70±17.01), the proportion of F4/80+ peritoneal macrophages was increased [(68.25±3.41)% vs. (50.84±4.98)%], while the ratio of F4/80+CD206+ anti-inflammatory peritoneal macrophages was decreased [(45.25±6.75)% vs. (66.66±3.36)%]. The α diversity sobs index of gut microbiota was downregulated significantly (118.50±23.25 vs. 255.70±6.87), the structure of species composition was altered, and the relative abundance of functional gut microbiota related to transcription, secondary metabolites biosynthesis, transport and catabolism, carbohydrate transport and metabolism, and signal transduction were decreased significantly in CLP group (all P < 0.05). Compared with CLP group, upon MSC or MSC-CM treatment, the pathological injury in lung and colon was alleviated to varying extent, the length of colon was increased (cm: 6.53±0.27, 6.87±0.18 vs. 6.00±0.26), the level of IL-1ß in serum was downregulated (ng/L: 382.10±16.93, 343.20±23.61 vs. 432.70±17.68), the ratio of F4/80+ peritoneal macrophages was decreased [(47.65±3.93)%, (48.68±2.51)% vs. (68.25±3.41)%], the ratio of F4/80+CD206+ anti-inflammatory peritoneal macrophages was increased [(52.73±5.02)%, (66.38±4.73)% vs. (45.25±6.75)%], and the α diversity sobs index of gut microbiota was increased (182.50±16.35, 214.00±31.18 vs. 118.50±23.25), and the effects of MSC-CM were more significant (all P < 0.05). At the same time, species composition of gut microbiota was rebuilt, and a tendency of increase in relative abundance of functional gut microbiota was observed upon MSC and MSC-CM treatment. CONCLUSIONS: Both MSC and MSC-CM could alleviate inflammatory injury in tissues, and showed regulatory effects on gut microbiota in septic mouse model, moreover, MSC-CM exhibited superior advantages over MSC.


Asunto(s)
Microbioma Gastrointestinal , Femenino , Animales , Ratones , Ratones Endogámicos C57BL , Medios de Cultivo Condicionados/farmacología , ARN Ribosómico 16S , Ciego , Modelos Animales de Enfermedad , Disnea
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(3): 278-286, 2023 Mar.
Artículo en Zh | MEDLINE | ID: mdl-36916341

RESUMEN

OBJECTIVE: To study the crosstalk between the activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1)-X-box binding protein 1 (XBP1) pathway in oxygen-glucose deprivation/reoxygenation (OGD/R)-injured mouse hippocampal neuronal cell line HT22. METHODS: The OGD/R-injured HT22 cell model was used to observe the changes of the indicators of endoplasmic reticulum stress (ERS), cell viability, and apoptosis at different OGD/R time points (0, 3, 6, 12, and 24 hours). HT22 cells in the logarithmic growth phase were randomized into blank control group, control+ATF6 activator (AA147) group, control+IRE1 inhibitor (4µ8c) group, OGD/R model group, OGD/R+AA147 group and OGD/R+4µ8c group (10 µmol/L AA147 or 16 µmol/L 4µ8c was given during the whole process in the AA147 group and 4µ8c group). Western blotting was used to detect the expression of ERS-related proteins [glucose-regulated protein 78 (GRP78), phosphorylated-inositol-requiring enzyme 1 (p-IRE1), and phosphorylated-eukaryotic translation initiation factor-2α (p-eIF2α)], and apoptosis-related proteins (Bcl-2, Bax, caspase-3, and cleaved caspase-3). The mRNA of ERS-related genes, and ATF6 [homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 (Herpud1), protein disulfide isomerase associated 4 (Pdia4) and Sel-1 suppressor of lin-12-like (Sel1L)] and spliced XBP1 [XBP1s, include DnaJ heat shock protein family member B9 (Erdj4), Sec24 related gene family, member D (Sec24d) and signal sequence receptor, gamma (Ssr3)] induced transcriptional response-related genes were measured by real-time quantitative polymerase chain reaction (RT-qPCR). A cell counting kit-8 (CCK-8) assay was used to detect the viability of HT22 cells. Immunofluorescence was utilized to test the expression of cleaved caspase-3. RESULTS: Compared with the blank control group, the expression of ERS-related proteins p-IRE1 and p-eIF2α were significantly increased at 12 hours and 3 hours following OGD/R, respectively (p-IRE1/ß-actin: 2.09±0.10 vs. 1.00±0.00, p-eIF2α/ß-actin: 1.39±0.11 vs. 1.00±0.00, both P < 0.01). The mRNA expressions of ERS-related genes [ATF6, XBP1s, unspliced XBP1 (XBP1u), activating transcription factor 4 (ATF4), CCAAT/EBP homologous protein (CHOP)] were also upregulated in different OGD/R timepoint in HT22 cells, which indicated ERS was activated in OGD/R-stimulated HT22 cells. Compared with the OGD/R model group, the expression of protein p-IRE1 was not changed, but the mRNA of XBP1s and XBP1u were obviously downregulated in the OGD/R+AA147 group [XBP1s (2-ΔΔCt): 0.76 (0.71, 0.92) vs. 1.13 (1.03, 1.29), XBP1u (2-ΔΔCt): 0.29±0.05 vs. 0.52±0.04, both P < 0.01], whereas the expressions of XBP1s-induced transcriptional response downstream genes did not change significantly. Compared with the OGD/R model group, the protein of short-form ATF6 (sATF6) and GRP78 were not changed after administration of 4µ8c, neither was the mRNA expression of ATF6-induced transcriptional response-related genes. These results showed that the mRNA expression of XBP1s and XBP1u were inhibited by AA147-induced activation of ATF6, but no crosstalk was observed between the transcriptional response induced by ATF6 and XBP1s. Compared with the blank control group, the cell viability decreased significantly at OGD/R 3 hours [(44.64±5.12) % vs. (99.13±5.76) %, P < 0.01], the ratios of apoptosis-related proteins Bax/Bcl-2 and cleaved caspase-3/caspase-3 were significantly increased at OGD/R 3 hours and OGD 0 hour, respectively (Bax/Bcl-2: 6.15±1.65 vs. 1.00±0.00, cleaved caspase-3/caspase-3: 17.48±2.75 vs. 1.00±0.00, both P < 0.01), which indicated that apoptosis was activated in OGD/R-treated HT22 cells. Compared with the OGD/R model group, the cell viability decreased significantly [(36.52±17.78)% vs. (69.90±9.43)%, P < 0.01], and the ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3 were significantly upregulated in the OGD/R+AA147 group in HT22 cells (Bax/Bcl-2: 2.06±0.31 vs. 1.10±0.25, cleaved caspase-3/caspase-3: 3.35±0.59 vs. 0.55±0.09, both P < 0.01). CONCLUSIONS: Under our experimental conditions, no obvious crosstalk between the transcriptional response induced by ATF6 and XBP1s was observed, while ATF6 activation induced by AA147 suppressed mRNA expression of XBP1s and XBP1u and promoted cell death in OGD/R-treated HT22 cells.


Asunto(s)
Factor de Transcripción Activador 6 , Neuronas , Proteína 1 de Unión a la X-Box , Animales , Ratones , Línea Celular , Factor de Transcripción Activador 6/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , Neuronas/metabolismo , Oxígeno , Glucosa , Apoptosis , Estrés del Retículo Endoplásmico , Supervivencia Celular , Chaperón BiP del Retículo Endoplásmico/metabolismo
7.
World J Emerg Med ; 14(1): 31-36, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36713335

RESUMEN

BACKGROUND: Remimazolam is a novel ultra-short-acting sedative, but its safety and adverse events (AEs) in high-risk patients in the intensive care unit (ICU) setting remain unknown. METHODS: This was a single-center, retrospective study that compared remimazolam to propofol and midazolam in patients undergoing upper gastrointestinal endoscopy. The primary outcome was the incidence of treatment-related AEs. The secondary outcomes were the time to extubation, the length of ICU stay, and the average cost of sedative per case. RESULTS: Of the 88 patients analyzed, 47 were treated with remimazolam (mean dose, 7.90±4.84 mg), and 41 were treated with propofol (21.19±17.98 mg) or midazolam (3.08±2.17 mg). There was no statistically significant difference in the average duration of the endoscopic procedure (35.89±13.37 min vs. 44.51±21.68 min, P=0.133) or the time to extubation (15.00±9.75 h vs. 20.59±18.71 h, P=0.211) in the remimazolam group (group I) compared to the propofol or midazolam group (group II). ICU stays (5.40±2.93 d vs. 4.63±3.31 d, P=0.072) and treatment-related AEs (48.61% vs. 51.38%, P=0.056) were similar between groups. The average cost of sedative per case was significantly lower in the group I than in the group II (RMB 16.07±10.58 yuan vs. RMB 24.37±15.46 yuan, P=0.016). CONCLUSION: Remimazolam-based sedation was noninferior to the classic sedatives and had lower average cost per case, indicating that it may be used as a promising sedative for high-risk patients during endoscopic procedures in the ICU setting.

8.
Pathol Res Pract ; 247: 154519, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37244049

RESUMEN

We explored the pathological changes and the activation of local complement system in COVID-19 pneumonia. Lung paraffin sections of COVID-19 infected patients were analyzed by HE (hematoxylin-eosin) staining. The deposition of complement C3, the deposition of C3b/iC3b/C3d and C5b-9, and the expression of complement regulatory proteins, CD59, CD46 and CD55 were detected by immunohistochemistry. In COVID-19 patients' lung tissues, fibrin exudation, mixed with erythrocyte, alveolar macrophage and shed pneumocyte are usually observed in the alveoli. The formation of an "alveolar emboli" structure may contribute to thrombosis and consolidation in lung tissue. In addition, we also found that compared to normal tissue, the lung tissues of COVID-19 patients displayed the hyper-activation of complement that is represented by extensive deposition of C3, C3b/iC3b/C3d and C5b-9, and the increased expression level of complement regulatory proteins CD55, and especially CD59 but not CD46. The thrombosis and consolidation in lung tissues may contribute to the pathogenesis of COVID-19. The increased expression of CD55 and CD59 may reflect a feedback of self-protection on the complement hyper-activation. Further, the increased C3 deposition and the strongly activated complement system in lung tissues may suggest the rationale of complement-targeted therapeutics in conquering COVID-19.


Asunto(s)
COVID-19 , Complejo de Ataque a Membrana del Sistema Complemento , Humanos , Proteína Cofactora de Membrana , Antígenos CD55 , Pulmón , Complemento C3b
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(9): 999-1003, 2022 Sep.
Artículo en Zh | MEDLINE | ID: mdl-36377459

RESUMEN

Ischemia/reperfusion (I/R) caused by cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) was the primary cause of post-cardiac arrest syndrome (PCAS), including post-cardiac arrest myocardial dysfunction and post-cardiac arrest brain injury. Disturbance of endoplasmic reticulum proteostasis, so-called endoplasmic reticulum stress (ERS) was one of the pathological changes induced by I/R injury. The unfolded protein response (UPR) was an adaptive response triggered by ERS in cells. Modulating the UPR arms to alleviate ERS to promote cell survival was promising for attenuating I/R injury. Activating the activating transcription factor6 (ATF6) signaling pathway, one of the arms of the UPR, confers protection against I/R injury in multiple tissues by restoring endoplasmic reticulum proteostasis and reducing oxygen free radicals. This article reviewed the structural characteristics and biological function of ATF6 and focused on its essential role in cardiac and cerebral I/R injury as well as potential therapeutic targets, hoping to provide new ideas for the effective treatment of PCAS.


Asunto(s)
Paro Cardíaco , Daño por Reperfusión , Humanos , Factor de Transcripción Activador 6/genética , Factor de Transcripción Activador 6/metabolismo , Factor de Transcripción Activador 6/farmacología , Apoptosis , Estrés del Retículo Endoplásmico/fisiología , Respuesta de Proteína Desplegada
10.
NPJ Parkinsons Dis ; 8(1): 1, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35013321

RESUMEN

The pathological hallmark of Parkinson's disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD.

11.
Front Pharmacol ; 13: 1028002, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36506549

RESUMEN

Ischemia/reperfusion caused by cardiac arrest (CA) disturbs endoplasmic reticulum (ER) homeostasis and redox balance in neurons. AA147, originally developed as a pharmacologic activator of the activating transcription factor 6 (ATF6), can protect multiple tissues from ischemia/reperfusion injury (IRI) by decreasing reactive oxygen species (ROS) and restoring ER function. However, it is unclear whether pharmacologic treatment of AA147 could ameliorate post-CA cerebral IRI and whether it is associated with proteostasis regulation and anti-oxidative stress mechanism. In the present study, mice were subjected to 9 min-CA surgery followed by cardiopulmonary resuscitation (CPR). AA147 or vehicle was administered 1 day before the operation and 15 min after the return of spontaneous circulation. We found that AA147 restored neurological function and reduced dead neurons in mice suffering from CA. Moreover, AA147 inhibited CA/CPR-caused neuronal apoptosis and ER stress, indicated by reduced TUNEL-positive neurons, surged expression of Bcl-2/Bax, and down expression of cleaved caspase-3, caspase-12, C/EBP homologous protein (CHOP). The expression of ATF6 and its regulated gene glucose-regulated protein 78 (GRP78) increased significantly after the administration of AA147, suggesting the activation of the ATF6 pathway. In addition, AA147 also alleviated the upsurge of the ROS generation and MDA levels as well as increased SOD activity, accompanied by enhancement of the nuclear factor E2-related factor 2 (Nrf2) and its modulated heme-oxygenase-1 (HO-1) expressions. Cotreatment of AA147 with inhibitors of the ATF6 or Nrf2 significantly suppressed AA147-dependent reductions in ROS scavenging and neuronal death after CA/CPR. The results suggested that AA147 could confer neuroprotection against post-CA cerebral IRI through inhibition of oxidative stress along with ER stress-associated apoptosis, which is attributed to the coregulation of both ATF6 and Nrf2 signaling pathways activity. Our findings support the potential for AA147 as a therapeutic approach to improve post-CA brain injury.

12.
Front Aging Neurosci ; 13: 760781, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34744697

RESUMEN

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. However, its cellular and molecular mechanisms still wrap in the mist. This is partially caused by the absence of appropriate animal models mimicking sporadic PD that constitutes the majority of cases. Previously, we reported that a cysteine protease, asparagine endopeptidase (AEP), is activated in an age-dependent manner, and cleaves α-synuclein in the brain of sporadic PD patients. The AEP-derived α-synuclein 1-103 fragment is required for the pathogenesis of PD. Thus, we designed and characterized a novel transgenic mouse line expressing α-synuclein 1-103 (designated N103 mice). This model shows an abundant accumulation of pathological α-synuclein in the central nervous system, loss of dopaminergic neurons in the substantia nigra, and progressive striatal synaptic degeneration. The N103 mice also manifest age-dependent PD-like behavioral impairments. Notably, the mice show weight loss and constipation, which are the common non-motor symptoms in PD. The RNA-sequencing analysis found that the transcriptomics pattern was extensively altered in N103 mice. In conclusion, the N103 mouse line, as a brand-new tool, might provide new insights into PD research.

13.
Medicine (Baltimore) ; 100(16): e25619, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879732

RESUMEN

ABSTRACT: The coronavirus disease (COVID-19) outbreak was first reported in December 2019 in Wuhan, China. Specific information about critically ill COVID-19 patients receiving invasive mechanical ventilation (IMV) is rare.To describe the clinical course and complications of critically ill patients with COVID-19 who received IMV and were successfully weaned from it.This retrospective study included patients admitted to 3 intensive care units (ICUs) and 1 sub-ICU of Renmin Hospital of Wuhan University and Wuhan Jin Yin-tan Hospital between December 24, 2019, and March 12, 2020. Eleven patients who had been diagnosed with critically ill COVID-19 according to the World Health Organization interim guidance, received invasive ventilation, and were finally successfully weaned from it, were enrolled in our study. Their presenting symptoms, comorbidity conditions, laboratory values, ICU course, ventilator parameters, treatments, and relative complications were recorded.Of 108 critically ill COVID-19 patients who received invasive ventilation, 11 patients who underwent tracheal extubation or terminal weaning were included. The mean age of the 11 patients was 52.8 years (range, 38-70 years), 8 (72.7%) were male, and 2 were health care workers. The median time from onset of symptoms to dyspnea was 6.6 days (range, 3-13 days), and the median duration of IMV was 15.7 days (range, 6-29 days). All 11 patients presented with acute severe hypoxemic respiratory failure and received IMV, and 1 patient switched to extracorporeal membrane oxygenation assistance. A lung-protective strategy with lower tidal volume ventilation and proper driving pressure is the main strategy of IMV. All patients had extrapulmonary manifestations, including acute kidney injury, hepatic dysfunction, myocardial damage, and/or lymphopenia. Hospital-acquired infections occurred in 7 (63.6%) patients.Critical COVID-19 illness is characterized by acute hypoxemic respiratory failure and subsequent dysfunction of other organs with a high mortality rate. Correct ventilation strategies and other clinical strategies to improve oxygenation based on the skilled trained group and the availability of equipment are the key methods to rescue lives.


Asunto(s)
Infecciones por Coronavirus/terapia , Cuidados Críticos/métodos , Respiración Artificial , Desconexión del Ventilador , Adulto , Anciano , China , Infecciones por Coronavirus/complicaciones , Oxigenación por Membrana Extracorpórea , Femenino , Humanos , Hipoxia/terapia , Hipoxia/virología , Masculino , Persona de Mediana Edad , Respiración Artificial/efectos adversos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/virología , Estudios Retrospectivos
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 336-340, 2020 Mar.
Artículo en Zh | MEDLINE | ID: mdl-32385999

RESUMEN

OBJECTIVE: To compare the severity of brain injury between asphyxia and electrical stimulation induced cardiac arrest in rats. METHODS: Forty-two healthy male Sprague-Dawley (SD) rats were randomized into sham group (n = 6), asphyxia group (n = 18) and electrical stimulation group (n = 18). Rats in each group were given invasive mechanical ventilation and femoral blood vessels catheterization for monitoring blood pressure and fluid infusion. In the asphyxia group, the tracheal tube was clamped to induce cardiac arrest, and in the electrical stimulation group, the esophageal electrical stimulation was used to induce cardiac arrest, and cardiopulmonary resuscitation (CPR) was performed 4 minutes after cardiac arrest. In the sham group, only tracheal intubation and femoral artery intubation were performed after anesthesia, but cardiac arrest was not induced. Animals were allowed to survive until 72 hours after resuscitation, and survival analysis was performed using Kaplan-Meier curves. At 24 hours and 72 hours after resuscitation, the neurological deficit score (NDS) was measured. The vena cava blood was collected, and the brain injury associated serum biomarkers, neuron-specific enolase (NSE) and S100B, were detected by enzyme-linked immunosorbent assay (ELISA). The brain tissues were then harvested to perform hematoxylin-eosin (HE) staining for observing pathological changes in the hippocampal CA1 area with light microscopy. RESULTS: Cardiac arrest was successfully induced in both the asphyxia group and the electrical stimulation group, 94.4% (17/18) and 88.9% (16/18) animals were resuscitated successfully in the two groups respectively. Kaplan-Meier curves analysis showed that 72-hour cumulative survival rate was similar in the asphyxia group and the electrical stimulation group (Log-Rank test: χ2 = 0.040, P = 0.841). Both asphyxia group and electrical stimulation group had higher NDS score than sham group at 24 hours after resuscitation (37.50±4.26, 32.17±4.02 vs. 8.33±2.33, both P < 0.01). NDS score showed a downwards trend at 72 hours after resuscitation in both model groups, and the decline was more significant in the electrical stimulation group, which was significantly different as compared with asphyxia group (14.00±2.89 vs. 26.33±4.84, P < 0.05). ELISA results showed that the levels of serum NSE at 24 hours after resuscitation in the asphyxia and electrical stimulation groups were significantly higher than those in the sham group (µg/L: 1.02±0.07, 1.02±0.02 vs. 0.87±0.02, both P < 0.05). NSE kept increasing at 72 hours after resuscitation in the asphyxia group, which showed significant difference as compared with sham group (µg/L: 1.03±0.05 vs. 0.87±0.02, P < 0.01). But it had almost recovered to the normal level in the electrical stimulation group without significant difference as compared with sham group (µg/L: 0.96±0.04 vs. 0.87±0.02, P > 0.05). There was no significant difference in S100B level at different time points after resuscitation among three groups. It was displayed under light microscope that there was no significant neuronal damage in the hippocampal CA1 area in the two model groups at 24 hours after resuscitation as compared with the sham group. At 72 hours, there were certain damages in the hippocampal CA1 area in both model groups, which were more obvious in the asphyxia group. CONCLUSIONS: Both cardiac arrest models induced by asphyxia and electrical stimulation show a certain degree of brain injuries after resuscitation. Brain injuries are more severe in asphyxia-induced cardiac arrest compared with trans-esophageal electrical stimulation method.


Asunto(s)
Lesiones Encefálicas , Reanimación Cardiopulmonar , Paro Cardíaco , Animales , Asfixia , Modelos Animales de Enfermedad , Estimulación Eléctrica , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(6): 677-680, 2020 Jun.
Artículo en Zh | MEDLINE | ID: mdl-32684211

RESUMEN

OBJECTIVE: To compare the therapeutic effects and safety of dexmedetomidine and midazolam on patients with severe coronavirus disease 2019 (COVID-19) who received non-invasive ventilation. METHODS: Patients with COVID-19 who needed non-invasive ventilation in one critical care medicine ward of Wuhan Jinyintan Hospital during the team support period from the department of critical care medicine of Renmin Hospital of Wuhan University from January 23rd to February 15th in 2020 were investigated retrospectively. Ramsay score, mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), arterial oxygen partial pressure (PaO2) before sedation and at 1, 12, 24 hours after sedation, sleep time were collected, and the side effects such as excessive sedation, fall of tongue, abdominal distension, aspiration, bradycardia, escalation to invasive mechanical ventilation during 24 hours were also collected. According to different sedative drugs, patients were divided into the control group (without sedative drugs), dexmedetomidine group and midazolam group. The changes of indicators among the three groups were compared. RESULTS: Fourteen patients were injected with dexmedetomidine (loading dose of 1 µg/kg for 10 minutes, maintained at 0.2-0.7 µg×kg-1×h-1); 9 patients were injected with midazolam (loading dose of 0.05 mg/kg for 2 minutes, maintained at 0.02-0.10 mg×kg-1×h-1); 12 patients didn't use sedative drugs due to limitations of previous hospital or patients' rejection. In dexmedetomidine group and midazolam group, the Ramsay score was maintained at 2-3 points after sedation, which were higher than those of control group at different time points after sedation, and there was no significant difference between dexmedetomidine group and midazolam group. MAP of dexmedetomidine group and midazolam group decreased gradually after sedation. MAP after 1-hour sedation was significantly lower than that before sedation, and MAP after 24 hours sedation was significantly lower than that in the control group [mmHg (1 mmHg = 0.133 kPa): 109.7±11.5, 107.1±12.3 vs. 121.1±13.3, both P < 0.05]. HR decreased gradually after sedation treatment, which was significantly lower after 12 hours of sedation than that before sedation, and HR in dexmedetomidine group was significantly lower than that in control group after 12 hours of sedation (bpm: 84.0±13.9 vs. 92.8±15.4 at 12 hours; 81.0±16.7 vs 92.6±12.7 at 24 hours, both P < 0.05). PaO2 increased and RR decreased in all three groups after ventilation. PaO2 in dexmedetomidine group and midazolam group were significantly higher than that in the control group after 12 hours of sedation [cmH2O (1 cmH2O = 0.098 kPa): 79.0±6.5, 79.0±8.9 vs. 70.0±7.8, both P < 0.05]; the decreases of RR in dexmedetomidine group and midazolam group were significant than that in control group after 1 hour of sedation (bpm: 34.0±3.9, 33.8±4.6 vs. 39.0±3.6, both P < 0.05). There were no differences of MAP, HR, PaO2 and RR between dexmedetomidine group and midazolam group at different time points. The sleep duration in dexmedetomidine group and midazolam group were significantly longer than that in the control group (hours: 4.9±1.9, 5.8±2.4 vs. 3.0±1.8, both P < 0.05), but there was no difference between dexmedetomidine group and midazolam group (P > 0.05). Adverse events occurred in all three groups. In midazolam group, there were 2 cases of excessive sedation with fall of tongue and abdominal distension, including 1 case of aspiration, 1 case receiving intubation due to refractory hypoxemia and 1 case due to unconsciousness. In dexmedetomidine group, there were 2 cases of bradycardia, 1 case of intubation due to refractory hypoxemia. In control group, 4 cases underwent intubation due to refractory hypoxemia. CONCLUSIONS: Non-invasive mechanical ventilation is an important respiratory support technology for patients with severe COVID-19. Appropriate sedation can increase the efficiency of non-invasive mechanical ventilation. Dexmedetomidine is more effective and safer than midazolam in these patients, but attention should be paid to HR and blood pressure monitoring.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Dexmedetomidina/uso terapéutico , Midazolam/uso terapéutico , Ventilación no Invasiva , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/terapia , Humanos , Hipnóticos y Sedantes , Unidades de Cuidados Intensivos , Neumonía Viral/terapia , Estudios Retrospectivos , SARS-CoV-2
16.
Lancet Respir Med ; 8(5): 475-481, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32105632

RESUMEN

BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/aislamiento & purificación , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Enfermedad Crítica , Femenino , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Respiración Artificial/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/virología , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento
17.
Ann Intensive Care ; 10(1): 73, 2020 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-32506258

RESUMEN

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed. METHODS: Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences. RESULTS: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations. CONCLUSION: There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.

18.
Front Med (Lausanne) ; 7: 611460, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33511146

RESUMEN

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

19.
Front Med (Lausanne) ; 7: 615845, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33425960

RESUMEN

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies. Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days). Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3-27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy. Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

20.
Mil Med Res ; 7(1): 41, 2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32887670

RESUMEN

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Asunto(s)
Quimioprevención/métodos , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adulto , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Alta del Paciente/normas , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Guías de Práctica Clínica como Asunto , SARS-CoV-2
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