RESUMEN
Yellowhorn (Xanthoceras sorbifolium) is a deciduous shrub or small tree native to China. The content of oil in kernels is 52.7% to 58.0%, of which is the source of neuroic acid (3.7-4.4%). (Liang et al. 2022). In recent years, yellowhorn, as a woody oleiferous crop, has been cultivated in northern China (Xiao et al. 2023). In late June 2019, an unknown collar rot was observed on yellowhorn in Tai'an, and Weifang City, Shandong Province, China. Infected plants had dark brown to black lesions at the base of the stem, about 10 to 15 cm from the ground, bark dehiscence and rot, resulting in wilting, withering, and death of plants. The disease incidence in the field was 35-48%. Representative symptomatic samples were collected randomly from the collar of 8 plants, and 24 samples were cut from the diseased tissue into 5 mm square pieces, surface disinfected with 75% alcohol for 30s and then with 0.1% mercury bichloride for 1min, plated onto potato dextrose agar (PDA), and incubated at 28°C in the dark for 2 to 3 days. Isolation frequency of the pathogen from symptomatic collar was 83.3%. The colonies were subcultured three times on PDA to obtained the purified colonies. The colonies appeared flocculent mycelia incubated on PDA at 28°C for 7 days. The color of the surface and the reverse colony was white and cream, respectively. The chlamydosposres were smooth with thick walled, and are formed singly. Microconidia were oval or ellipsoidal, with 0-1 septum; macroconidia end cells curved to slightly, with 3- or 5-septate, and measured 17.3 to 23.1 × 4.9 to 6.5 µm (avg. 21.3 × 5.9 µm, n = 60). The morphological characteristics fit the descriptions of Fusarium spp. (Hafizi et al. 2013; Crespo et al 2019). Genomic DNA extracted from four representative isolates (XSTA4, XSTA7, XSWF6 and XSWF8), and the internal transcribed spacer region (ITS) of ribosomal DNA, translation elongation factor 1-alpha (EF1-α), RNA polymerase I beta subunit (RPB1), and RNA polymerase II beta subunit (RPB2) genes were amplified using the primer pairs ITS1/ITS4 (White et al. 1990), EF-1/EF-2, RPB-1F/1R, and RPB2-5F2/11aR (O'Donnell et al 2010), respectively. Amplicons were sequenced and compared in GenBank using a BLAST analysis. The ITS sequences (OR672118, OR669008, OR669039, and OR669279) had 100% similarity with the sequences of F. solani (MT560378, MG561938, MN989030 and OP630608, respectively). The EF1-α sequences (OR934984, OR934985, OR934986, and OR934987) matched 100% with the sequences of F. solani (OQ511088, MW332044, MW620166 and MT379886). The RPB-1 sequences (PP896852, PP896853, PP896854, and PP896855) had 100% similarity with the sequences of F. solani (OL474057, OR916019, MT305118 and MT305118, respectively). The RPB2 sequences (PP896856, PP896857, PP896858, and PP896859) matched 100% with the sequences of F. solani (OR371884, OK880266, OP784447 and OL474055, respectively). A phylogenetic analysis based on ITS, RPB2 and EF1-α sequences placed the four obtained isolates within the same clade containing the F. solani isolates A6, 91-84-1 and UCR1780. Pathogenicity tests were carried out in late-June 2020. Fifty 120-day-old healthy seedlings were wounded with 2 mm deep at stems in the collar region of plants at 5 cm above the soil for tested. The seedlings were inoculated on the wound with 3-mm mycelial discs from a 7-day-old culture of each four representative strains of 10 repeated, respectively. Ten seedlings inoculated on the wound with sterile PDA served as control. All plants were grown in an incubator with a 28°C temperature. After 20 days, the stems which were inoculated the representative strain turned brown, with 2 - 5 cm length lesion, and the plants developed typical wilting and withering symptoms which similar to those observed in the field. The control remained asymptomatic. The pathogen was reisolated from the inoculated stems and its identity confirmed with both morphology and using molecular tools. These results indicated that the pathogens of yellowhorn collar rot is F. solani. To our knowledge, this is the first report of F. solani causing collar rot of yellowhorn in China.
RESUMEN
RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Infecciones por Coronavirus/epidemiología , Mortalidad Hospitalaria , Hipertensión/epidemiología , Neumonía Viral/epidemiología , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , COVID-19 , Infecciones por Coronavirus/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicacionesRESUMEN
BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Hígado/fisiopatología , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Adulto , Anciano , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biomarcadores , COVID-19 , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal disability and death. As a derivative of N-acetylserotonin, N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC) can easily cross the blood-brain barrier and have a long half-life in the brain. In this study, the hypothesis was verified that HIOC plays a neuroprotective role in the HIE model and its potential mechanism was evaluated. Firstly, an HIE rat model was established to deliver HIOC, revealing that it can reduce cerebral infarction volume, cerebral edema, and neuronal apoptosis. The results of immunofluorescence staining, Western blots and RT-PCR further showed that HIOC could inhibit the activation of the NLRP3 inflammasome and the expression of related proteins. Finally, the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by HIOC was verified in vitro and in vivo. It was discovered that HIOC could increase the nuclear translocation of Nrf2, and that this induction can be reversed by the PI3K/Akt pathway inhibitor LY294002. In general terms, the neuroprotective effect of HIOC was confirmed in the HIE model, which is related to the activation of the Pi3k/Akt/Nrf2 signal pathway and the inhibition of the NLRP3 inflammasome.
Asunto(s)
Hipoxia-Isquemia Encefálica , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Fármacos Neuroprotectores , Serotonina , Transducción de Señal , Animales , Apoptosis/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/patología , Inflamasomas/antagonistas & inhibidores , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Serotonina/análogos & derivados , Serotonina/uso terapéutico , Transducción de Señal/efectos de los fármacos , Factor 2 Relacionado con NF-E2RESUMEN
Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.
Asunto(s)
COVID-19/mortalidad , Hiperlipidemias/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/terapia , Enfermedades Cardiovasculares/complicaciones , Estudios de Casos y Controles , Causas de Muerte , China/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process. A HIBD model in rat pups and a HI model in rat primary cerebrocortical neurons were established. Autophagy was evaluated by western blot. The HIBD in rats was evaluated by hematoxylin and eosin staining, TUNEL staining, triphenyl tetrazolium chloride staining, and morris water maze test. The HI injury in vitro was evaluated by determining cell viability and apoptosis. The results showed that CRNDE expression was time-dependently increased in the brain after HIBD. Administration with CRNDE shRNA-expressing lentiviruses alleviated pathological injury and apoptosis in rat hippocampus, decreased infarct volume, and improved behavior performance of rats subjected to HIBD. Furthermore, CRNDE silencing promoted cell viability and inhibited cell apoptosis in neurons exposed to HI. Moreover, CRNDE silencing promoted autophagy and the autophagy inhibitor 3-methyladenine counteracted the neuroprotective effect of CRNDE silencing on HI-induced neuronal injury both in vivo and in vitro. Collectively, CRNDE silencing alleviates HIBD, at least partially, through promoting autophagy.
Asunto(s)
Autofagia , Encéfalo/metabolismo , Hipoxia-Isquemia Encefálica/prevención & control , Neuronas/metabolismo , Fármacos Neuroprotectores , ARN Largo no Codificante/antagonistas & inhibidores , Animales , Animales Recién Nacidos , Conducta Animal , Encéfalo/patología , Hipoxia-Isquemia Encefálica/etiología , Hipoxia-Isquemia Encefálica/patología , Neuronas/patología , ARN Largo no Codificante/genética , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: This study aimed to test the hypothesis that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) could exacerbate brain injury caused by intrauterine infection in neonatal rats. METHODS: Intrauterine infection was induced in pregnant rats by lipopolysaccharide (LPS). After delivery, newborn rats with brain injury caused by intrauterine infection were randomly divided into control, control shRNA, and CRNDE shRNA groups. CRNDE expression in serum and amniotic fluid of pregnant rats and neonatal brain tissues were determined by quantitative real-time PCR (qRT-PCR). Morris water maze (MWM) task was used to test the spatial learning and memory ability. Histological examination and apoptosis detection were performed by hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Immunohistochemistry was conducted to evaluate the activation of astrocytes and microglia. RESULTS: LncRNA CRNDE was highly expressed in serum and amniotic fluid of maternal rats and in brain tissues of offspring rats. Furthermore, shRNA-mediated CRNDE downregulation could rescue the spatial learning and memory ability, improve brain histopathological changes and cell death, and inhibit the activation of astrocytes and microglia caused by LPS. CONCLUSION: CRNDE silencing possessed a cerebral protective effect in neonatal rats with brain injury caused by interauterine infection.
Asunto(s)
Lesiones Encefálicas/etiología , Lesiones Encefálicas/genética , ARN Largo no Codificante/metabolismo , Útero/microbiología , Útero/patología , Animales , Animales Recién Nacidos , Astrocitos/patología , Encéfalo/patología , Lesiones Encefálicas/fisiopatología , Muerte Celular , Citocinas/biosíntesis , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Lipopolisacáridos , Masculino , Memoria , Microglía/patología , Embarazo , ARN Largo no Codificante/genética , Ratas , Aprendizaje Espacial , Regulación hacia Arriba/genéticaRESUMEN
Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low-density lipoprotein (ox-LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox-LDL was able to trigger human macrophages THP-1 cells, a human monocytic cell line, apoptosis in a dose-dependent and time-dependent course. In addition, we observed that NEAT1 was significantly increased in THP-1 cells incubated with ox-LDL and meanwhile miR-342-3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP-1 cells. As exhibited, CD36, oil-red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP-1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL-6), IL-1ß, cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-α) protein levels were remarkably depressed by NEAT1 siRNA in THP-1 cells. By using bioinformatics analysis, miR-342-3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR-342-3p could also greatly suppress inflammation response and lipid uptake in THP-1 cells. Knockdown of NEAT1 and miR-342-3p mimics inhibited lipid uptake in THP-1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR-342-3p in human macrophages THP-1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.
Asunto(s)
Aterosclerosis/metabolismo , Colesterol/sangre , Mediadores de Inflamación/metabolismo , Lipoproteínas LDL/farmacología , Macrófagos/efectos de los fármacos , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Apoptosis/efectos de los fármacos , Aterosclerosis/patología , Transporte Biológico , Regulación de la Expresión Génica , Humanos , Macrófagos/metabolismo , Macrófagos/patología , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/genética , Transducción de Señal , Células THP-1RESUMEN
OBJECTIVE: Periventricular-intraventricular hemorrhage is the most common type of intracranial bleeding in newborns, especially in the first 3 days after birth. Severe periventricular-intraventricular hemorrhage is considered a progression from mild periventricular-intraventricular hemorrhage and is often closely associated with severe neurological sequelae. However, no specific indicators are available to predict the progression from mild to severe periventricular-intraventricular in early admission. This study aims to establish an early diagnostic prediction model for severe PIVH. METHOD: This study was a retrospective cohort study with data collected from the MIMIC-III (v1.4) database. Laboratory and clinical data collected within the first 24 h of NICU admission have been used as variables for both univariate and multivariate logistic regression analyses to construct a nomogram-based early prediction model for severe periventricular-intraventricular hemorrhage and subsequently validated. RESULTS: A predictive model was established and represented by a nomogram, it comprised three variables: output, lowest platelet count and use of vasoactive drugs within 24 h of NICU admission. The model's predictive performance showed by the calculated area under the curve was 0.792, indicating good discriminatory power. The calibration plot demonstrated good calibration between observed and predicted outcomes, and the Hosmer-Lemeshow test showed high consistency (p = 0.990). Internal validation showed the calculated area under a curve of 0.788. CONCLUSIONS: This severe PIVH predictive model, established by three easily obtainable indicators within the NICU, demonstrated good predictive ability. It offered a more user-friendly and convenient option for neonatologists.
Asunto(s)
Hemorragia Cerebral Intraventricular , Nomogramas , Humanos , Recién Nacido , Estudios Retrospectivos , Femenino , Masculino , Hemorragia Cerebral Intraventricular/diagnóstico , Índice de Severidad de la Enfermedad , Bases de Datos Factuales , Hemorragia Cerebral/diagnóstico , Valor Predictivo de las Pruebas , Recuento de PlaquetasRESUMEN
Hypoxic-ischemic brain damage (HIBD) is one of the major causes of infant death and long-term neurological disturbances, which puts great pressure on families and society. Previous studies have reported that neuroinflammation regulates the pathogenesis of HIBD. MiR-155 has been reported to participate in many brain injuries; however, its direct implication and related mechanisms are not illuminated in HIBD. Herein, we identified that miR-155 plays a vital role in HIBD both in in vitro and in vivo models. We found that miR-155 promoted inflammation and apoptosis via targeting SIRT1 and negatively regulated its expression levels in oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vitro model. Silencing of SIRT1 reversed the effects of miR-155 inhibitor on apoptosis and the NF-κB pathway in OGD/R-treated PC12 cells and microglia (BV2) cells. Moreover, in a neonatal rat HIBD model, miR-155 enhanced apoptosis and inflammation in the brains of rats with HIBD in vivo. Together, our results demonstrated that miR-155 exerted a negative effect in HIBD by targeting SIRT1, which could contribute to the treatment of neonatal patients with hypoxic-ischemic brain damage.
Asunto(s)
Hipoxia-Isquemia Encefálica , MicroARNs , Ratas , Animales , Sirtuina 1/metabolismo , Hipoxia-Isquemia Encefálica/metabolismo , Oxígeno/farmacología , Encéfalo/metabolismo , Apoptosis , MicroARNs/metabolismo , Inflamación , Animales Recién NacidosRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49-75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. METHODS: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. RESULTS: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00-56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. CONCLUSIONS: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.
Asunto(s)
COVID-19 , Humanos , Masculino , Persona de Mediana Edad , Saturación de Oxígeno , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
PURPOSE: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD). PATIENTS AND METHODS: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers. RESULTS: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49-4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21-183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01-0.56; P < 0.001). CONCLUSION: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.
RESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. METHODS: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. FINDINGS: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. CONCLUSIONS: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. FUNDING: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.
Asunto(s)
Lesión Renal Aguda , COVID-19 , Lesión Renal Aguda/diagnóstico , COVID-19/epidemiología , Femenino , Humanos , Riñón , Masculino , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). METHODS: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). FINDINGS: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. CONCLUSIONS: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. FUNDING: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).
Asunto(s)
COVID-19 , Recuento de Células Sanguíneas , Mortalidad Hospitalaria , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.
Asunto(s)
Corticoesteroides/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Linfocitos/citología , Neutrófilos/citología , Corticoesteroides/efectos adversos , Área Bajo la Curva , COVID-19/mortalidad , COVID-19/patología , COVID-19/virología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/patología , Tiempo de Internación , Modelos de Riesgos Proporcionales , Curva ROC , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.
Asunto(s)
COVID-19 , Medición de Riesgo/métodos , COVID-19/epidemiología , COVID-19/mortalidad , China , Hospitalización/estadística & datos numéricos , Humanos , Italia , Factores de RiesgoRESUMEN
Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and neuroprotective effects. It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms. We explored the effects of glucagon-like peptide-1 receptor on nociception, cognition, and neuroinflammation in chronic pain. A rat model of chronic pain was established using left L5 spinal nerve ligation. The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation. Electrophysiological examinations showed that, after treatment with exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6. All of these effects could be reversed by exendin-4 treatment. These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.
RESUMEN
The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.
Asunto(s)
Acidosis/inducido químicamente , Infecciones por Coronavirus/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Metformina/efectos adversos , Neumonía Viral/complicaciones , Acidosis Láctica/inducido químicamente , Anciano , COVID-19 , China/epidemiología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Hospitalización , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Estudios RetrospectivosRESUMEN
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.