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1.
Genetics ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792683

RESUMO

Break-induced replication (BIR) is essential for the repair of DNA double-strand breaks (DSBs) with single ends. DSBs-induced microhomology-mediated BIR (mmBIR) and template-switching can increase the risk of complex genome rearrangement. In addition, DSBs can also induce the multi-invasion-mediated DSB amplification. The mmBIR-induced genomic rearrangement has been identified in cancer cells and patients with rare diseases. However, when and how mmBIR are initiated haven't been fully and deeply studied. Furthermore, it is not well understood about the conditions for initiation of multi-invasion-mediated DSB amplification. In the G2 phase oocyte of mouse, we identified a type of short scale BIR (ssBIR) using the DNA replication indicator 5-ethynyl-2´-deoxyuridine (EdU). These ssBIRs could only be induced in the fully-grown oocytes but not the growing oocytes. If the DSB oocytes were treated with Rad51 or Chek1/2 inhibitors, both EdU signals and DSB marker γH2A.X foci would decrease. In addition, the DNA polymerase inhibitor Aphidicolin could inhibit the ssBIR and another inhibitor ddATP could reduce the number of γH2A.X foci in the DSB oocytes. In conclusion, our results showed that DNA DSBs in the fully-grown oocytes can initiate ssBIR and be amplified by Rad51 or DNA replication.

2.
Int J Oral Sci ; 13(1): 8, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692335

RESUMO

Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.

3.
Ying Yong Sheng Tai Xue Bao ; 32(3): 1033-1044, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754570

RESUMO

The demonstration area of ecologically friendly development in the Yangtze River Delta is a major national strategy area, and thus eco-environmental protection should be a priority for the sustainable development. Exploring the spatial-temporal variations of franctional vegetation coverage (FVC) is conducive to accurate assessing the ecological quality of environment, which is of great significance to regional sustainable development. In this study, the characteristics and trends of spatial-temporal variation of vegetation cover during 1984-2019 in the demonstration area were analyzed based on Google Earth Engine (GEE). The effects of different ecological factors on FVC were quantified by the boosted regression tree (BRT). Results showed that,the changing trend of FVC in the study area shifted from decreasing to increasing trend from 1984 to 2019. The spatial distribution of FVC in the study area varied with both stages and regions. FVC was mainly degraded. Compared with the year 1984, the area of vegetation degradation and improvement in 2019 accounted for 49.8% and 12.8%, respectively. The vegetation degradation mainly occurred in the north of Wujiang, south of Jiashan, and northeast of Qingpu. Human activities severely weakened the influence of natural factors on FVC. Our findings suggested that the GEE is an effective tool for monitoring the dynamics of vegetation coverage.


Assuntos
Ecossistema , Rios , China , Conservação dos Recursos Naturais , Monitoramento Ambiental , Humanos
4.
BMC Womens Health ; 21(1): 88, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648484

RESUMO

BACKGROUND: The present study aims to provide a comparative analysis of the etiologies of female infertility between Dehong, on the Yunnan Frontier, and Kunming. METHODS: A retrospective study, which included 941 infertile females in Kunming who were treated in the First People's Hospital of Yunnan Province and infertile females who were treated in the local hospital in Dehong from January 2016 to November 2018, was conducted. A comparative analysis of the etiologies of infertility in the two regions was then carried out. RESULTS: In patients with primary infertility, ovulation disorder (15.03%) was the main cause of infertility in Kunming, and pelvic inflammatory disease (25.59%) was the main cause in Dehong. With regard to secondary infertility, although pelvic inflammatory disease was the main cause of infertility in both regions, the incidence of intrauterine adhesions in Kunming was significantly higher than in Dehong. CONCLUSIONS: The etiology of infertility showed different epidemiological characteristics depending on the region, hence individualized treatment should be given accordingly.

5.
Nat Commun ; 12(1): 1806, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753733

RESUMO

Better diagnostic tools are needed to combat the ongoing COVID-19 pandemic. Here, to meet this urgent demand, we report a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This serological assay, called SATiN, is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in the liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that SATiN has a similar sensitivity to ELISA, and its readouts are consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics, as well as disease and vaccination management.

6.
Plant Cell ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33604650

RESUMO

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.

7.
Dev Cell ; 56(5): 702-715.e8, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609462

RESUMO

N6-methyladenosine (m6A), one of the most prevalent RNA post-transcriptional modifications, is involved in numerous biological processes. In previous studies, the functions of m6A were typically identified by perturbing the activity of the methyltransferase complex. Here, we dissect the contribution of m6A to an individual-long noncoding RNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). The mutant MALAT1 lacking m6A-motifs significantly suppressed the metastatic potential of cancer cells both in vitro and in vivo in mouse. Super-resolution imaging showed that the concatenated m6A residues on MALAT1 acted as a scaffold for recruiting YTH-domain-containing protein 1 (YTHDC1) to nuclear speckles. We further reveal that the recognition of MALAT1-m6A by YTHDC1 played a critical role in maintaining the composition and genomic binding sites of nuclear speckles, which regulate the expression of several key oncogenes. Furthermore, artificially tethering YTHDC1 onto m6A-deficient MALAT1 largely rescues the metastatic potential of cancer cells.

8.
IEEE Trans Cybern ; PP2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502988

RESUMO

Fault detection for distributed parameter processes (heat processes, fluid processes, etc.) is vital for safe and efficient operation. On one hand, the existing data-driven methods neglect the evolution dynamics of the processes and cannot guarantee that they work for highly dynamic or transient processes; on the other hand, model-based methods reported so far are mostly based on the backstepping technique, which does not possess enough redundancy for fault detection since only the boundary measurement is considered. Motivated by these considerations, we intend to investigate the robust fault detection problem for distributed parameter processes in a model-based perspective covering both boundary and in-domain measurement cases. A real-time fault detection filter (FDF) is presented, which gets rid of a large amount of data collection and offline training procedures. Rigorous theoretic analysis is presented for guiding the parameters selection and threshold computation. A time-varying threshold is designed such that the false alarm in the transient stage can be avoided. Successful application results on a hot strip mill cooling system demonstrate the potential for real industrial applications.

9.
Cancer Cell Int ; 21(1): 71, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482821

RESUMO

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

10.
Microsc Microanal ; : 1-11, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33478599

RESUMO

Somatic cell nuclear transfer (SCNT) holds vast potential in agriculture. However, its applications are still limited by its low efficiency. Histone 3 lysine 9 trimethylation (H3K9me3) was identified as an epigenetic barrier for this. Histone demethylase KDM4D could regulate the level of H3K9me3. However, its effects on buffalo SCNT embryos are still unclear. Thus, we performed this study to explore the effects and underlying mechanism of KDM4D on buffalo SCNT embryos. The results revealed that compared with the IVF embryos, the expression level of KDM4D in SCNT embryos was significantly lower at 8- and 16-cell stage, while the level of H3K9me3 in SCNT embryos was significantly higher at 2-cell, 8-cell, and blastocyst stage. Microinjection of KDM4D mRNA could promote the developmental ability of buffalo SCNT embryos. Furthermore, the expression level of ZGA-related genes such as ZSCAN5B, SNAI1, eIF-3a, and TRC at the 8-cell stage was significantly increased. Meanwhile, the pluripotency-related genes like POU5F1, SOX2, and NANOG were also significantly promoted at the blastocyst stage. The results were reversed after KDM4D was inhibited. Altogether, these results revealed that KDM4D could correct the H3K9me3 level, increase the expression level of ZGA and pluripotency-related genes, and finally, promote the developmental competence of buffalo SCNT embryos.

11.
Exp Eye Res ; 204: 108450, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33497690

RESUMO

PURPOSE: This study examined the patterned treatment of corneal collagen cross-linking (CXL) for keratoconus to reduce the complications caused by ultraviolet (UV) irradiation. By modifying the method of UV irradiation during the cross-linking process, cross-linking with a special structure is achieved, and the cross-linking effect is analyzed and compared to that of traditional cross-linking. By constructing an animal model of keratoconus, the process and effect of corneal cross-linking can be investigated more fundamentally. These studies provide valuable references for future cross-linking precision improvement and specialization. METHOD: By injecting exogenous collagenase into the corneal stroma of rabbits, the balance between collagenase and collagenase inhibitor in the corneal stroma was disrupted, the collagen fiber structure of the cornea was broken to simulate the pathogenesis of keratoconus, and an animal model of keratoconus was thus constructed. Two custom cross-linking patterns were designed with reference to the cable dome structure, and these two special patterns were irradiated and cross-linked by a DMD chip. The cross-linking effect was evaluated by optical coherence tomography (OCT), corneal topography and corneal biaxial tensile tests. The experimental rabbits were divided into four groups: group A, cross-linking of the bird's nest structure; group B, cross-linking of the honeycomb structure; group C, cross-linking of the traditional spot structure; and group D, normal (without modeling and cross-linking). RESULT: Following collagenase treatment, the collagen fiber structure of the rabbit cornea was destroyed, the central thickness of the cornea was reduced, the mechanical properties of the cornea were weakened, and no keratitis, ulcers or haze occurred. After the three cross-linking treatments, the morphology of the cornea improved, the density of the stromal layer increased, and the mechanical properties were enhanced. For the improvement of keratoconus mechanical properties, the average relative difference (Δ) of the four outcome measures was 61.98% for bird's nest cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.024), 16.13% for honeycomb cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.025), and 21.07% for traditional spot cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.014). All these differences are statistically significant. CONCLUSION: All three methods of cross-linking can improve the morphology and tissue structure of keratoconus and significantly improve the biomechanical properties of the cornea. Among them, the corneal cross-linking of the bird's nest structure attains the best biomechanical properties, followed by the corneal cross-linking of the traditional spot structure and of the honeycomb structure. This suggests that similar or better cross-linking effects can be achieved by designing custom structures with less UV exposure. This provides a direction for future research on better and more accurate pattern cross-linking treatments.

12.
Dev Dyn ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449399

RESUMO

BACKGROUND: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos. RESULTS: By weighted gene-coexpression network analysis, we found that cynomolgus gene networks have greater conservation with human embryos including a greater number of conserved hub genes than that of mouse embryos. Consistently, we found that early ICM/TE lineage-segregating genes in monkeys exhibit greater similarity with human when compared to mouse, so are the genes in signaling pathways such as LRP1 and TCF7 involving in WNT pathway. Last, we tested the role of one conserved pre-EGA hub gene, SIN3A, using a morpholino knockdown of maternal RNA transcripts in monkey embryos followed by single-cell RNA-seq. We found that SIN3A knockdown disrupts the gene-silencing program during the embryonic genome activation transition and results in developmental delay of cynomolgus embryos. CONCLUSION: Taken together, our study provided new insight into evolutionarily conserved and divergent transcriptome dynamics during mammalian preimplantation development.

13.
Gynecol Endocrinol ; 37(4): 353-357, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33491494

RESUMO

AIMS: Our study was to evaluate the benefits of human umbilical cord mesenchymal stem cells (hUCMSCs) for the prevention of premature ovarian failure (POF) in a rat model. MATERIALS AND METHODS: 80 female SD rats aged between 6 and 8 weeks were randomly divided into 4 groups A, B, C and D. Rats in group A is normal control group; group B, C and D received zona pellucida glycoprotein 3 (pZP3) administration to induce POF model. Among these, group B is model control group; group C received PBS injection in ovaries and group D received hUCMSCs injection in ovaries, all injections were performed after modeling on the same day. Estrus cycle; serum hormone level of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and amount of ovarian follicles were detected 20 days after treatment. RESULTS: We successfully injected hUCMSCs in the ovary tissue of a POF rat. The estrus cycle and hormone expression of the rats in group D tends to be normal. Histological studies indicated that hUCMSCs transplantation increased the amount of ovarian follicles. CONCLUSIONS: This study shows that hUCMSCs may have a preventive effect on POF rats.

14.
J Hazard Mater ; 403: 123692, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264883

RESUMO

Fluorine-containing sludge from semiconductor industries were one kind of hazardous wastes, there was hardly effective treatment to realize its safe disposal and utilization. This paper evaluated the potential of preparing cement clinker by adding the sludge into raw meal by a series of experiments. The results revealed 2.0 % addition of the sludge markedly improved the burnability of the produced clinker, and promoted the formation of alite with more amounts and smaller size, but the 5.0 % addition of the sludge resulted in the abundant formation of interstitial phases to inhibit the formation of alite and belite. The better workability was gained with the addition of 2.0 %, and the optimal 28 d compressive strength was 50.76 MPa. The distribution of fluorine was higher in silicate phases, and it was mainly accumulated in the interfaces of silicate phases. Fluorine in the sludge was immobilized by calcium to form the binding forms of calcium fluoride in produced clinker and hydration products. The immobilization ratios of fluorine, copper, zinc and nickel were more than 99.5 %, and the addition of the sludge (≤5.0 %) into raw meal could not induce further environment hazards.

15.
Cell Cycle ; 19(24): 3521-3533, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33315498

RESUMO

ABBREVIATIONS: CCK8: Cell Counting Kit-8; CDK: cyclin-dependent kinase; DRD2: dopamine D2 receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H&E: hematoxylin and eosin; MMP: membrane potential; NAC: N-acetyl-L-cysteine; PI: Propidium iodide; Rh123: rhodamine-123; ROS: reactive oxygen species; TBST: tris-buffered saline containing 0.1% Tween 20 TNBC: Triple-negative breast cancer; Thi-hyd: Thioridazine hydrochloride.

16.
World Neurosurg ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33253953

RESUMO

The study drew attention to the application of functional magnetic resonance imaging (fMRI) and neuro-psychology in diagnosis of vascular mild cognitive impairment and the exploration of its relevant factors. Specifically, 28 patients with vascular cognitive impairment (VCI) were rolled inro an observation group, and 30 normal people were rolled into a control group. They all accepted MRI examination. The automatic segmentation algorithm based on graph theory was adopted to process the image. The age, gender, disease course, Montreal cognitive assessment (MoCA) score, regional homogeneity (ReHo), and low frequency amplitude (ALFF) levels were recorded. The results showed that there were no significant differences in age, gender, and course of disease between the observation group and the control group (P>0.05). The level of ReHo in the left posterior cerebellum of the observation group was significantly higher than that of the control group (P<0.05).The ReHo level of bilateral cingulate cortex was negatively correlated with MOCA score (P<0.05). The ALFF of bilateral inferior parietal lobe, parietal lobe, and prefrontal lobe in the observation group was significantly lower than that in the control group, and the ALFF of bilateral anterior cingulate gyrus, superior medial frontal gyrus, orbital frontal gyrus, right middle frontal gyrus, and right auxiliary motor area was higher than that in the control group (P<0.05) .Heart diseases such as myocardial infarction and atrial fibrillation are high risk factors for VCI. All in all, the fMRI combined with automatic segmentation algorithm can non-invasively observe the changes of the patient's brain tissue, which can be used in the recognition of VCI. The global network attributes of patients with depression tend to be more randomized and have stronger resilience under targeted attacks.

17.
Reprod Domest Anim ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219627

RESUMO

This study mainly explored the effects of Rapamycin on the growth of the Buffalo ear fibroblast (BEF) and embryonic developmental competence of somatic cell nuclear transfer (SCNT). The results show that the appropriate concentration (1 µM) of Rapamycin could significantly improve the proportion of the G0/G1 phase in BEF cells treated at a certain time (72 hr). Simultaneously, the percentage of the G0/G1 phase also was significantly higher than the serum starvation and control group. This may be related to Rapamycin inhibiting the phosphorylation of mTOR and affecting the expression of cell cycle-related genes (CDK2, CDK4, P27, CycleD1, and CycleD3). Besides, compared with the control group and serum-starved group, Rapamycin significantly decreased BEF cell apoptosis by reducing ROS generation. Moreover, these results also indicated that the proportion of BEF cells with normal chromosome multiples treated by Rapamycin is significantly higher than that of the serum-starved group (p < .05). Finally, this study explored the effects of Rapamycin and serum starvation on the embryonic developmental competence of SCNT. The results show that Rapamycin significantly increased the rate of 8-cell and blastocyst, compared with the control group and serum starvation group (p < .05). To summarize, these results indicate that Rapamycin improved the embryonic development competence of SCNT, which may be related to Rapamycin increasing the percentage of G0/G1 phase and maintaining BEF cell quality.

18.
Genes Nutr ; 15(1): 20, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238893

RESUMO

OBJECTIVE: This study aimed to quantitatively summarize the evidence for VDR BsmI gene polymorphism and osteoporosis risk in postmenopausal women. MATERIALS AND METHODS: The PubMed, EMBASE, Weipu, CNKI, and Wanfang databases were searched for eligible studies. Case-control studies containing available genotype frequencies of B/b were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: 4485 osteoporosis and 5490 controls were identified in our meta-analysis. In the stratified analysis, a significant association was observed between VDR BsmI gene polymorphism and osteoporosis susceptibility in Caucasians (additive model: OR = 0.809, 95% CI 0.678~0.965, p = 0.019; recessive model: OR = 0.736, 95% CI 0.568~0.955, p = 0.021; and co-dominant model: bb vs. BB OR = 0.701, 95% CI 0.511~0.962 p = 0.028), and we failed to find any significant relationship in Asians. CONCLUSION: The present meta-analysis suggests that VDR BsmI genotype is associated with increased risk of postmenopausal osteoporosis in Caucasians but not in Asians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VDR BsmI polymorphism and osteoporosis in postmenopausal women.

19.
Crit Care ; 24(1): 643, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172477

RESUMO

BACKGROUND: The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. METHODS: In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. RESULTS: A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0-3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0-80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0-12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. CONCLUSION: In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.


Assuntos
Corticosteroides/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pontuação de Propensão , /mortalidade , Idoso , Estudos de Coortes , Dexametasona/administração & dosagem , Feminino , Hospitalização/tendências , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Taxa de Sobrevida/tendências
20.
Signal Transduct Target Ther ; 5(1): 256, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139693

RESUMO

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spreading globally and poses a huge threat to human health. Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal-oral transmission route. In addition, there exist multiple abnormalities in liver enzymes. COVID-19-related liver injury may be due to drug-induced liver injury, systemic inflammatory reaction, and hypoxia-ischemia reperfusion injury. The direct toxic attack of SARS-CoV-2 on the liver is still questionable. This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Infecções por Coronavirus/epidemiologia , Gastroenteropatias/epidemiologia , Hepatopatias/epidemiologia , Pneumonia Viral/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Fezes/virologia , Gastroenteropatias/complicações , Gastroenteropatias/genética , Gastroenteropatias/virologia , Trato Gastrointestinal/lesões , Trato Gastrointestinal/patologia , Trato Gastrointestinal/virologia , Humanos , Fígado/fisiopatologia , Fígado/virologia , Hepatopatias/genética , Hepatopatias/patologia , Hepatopatias/virologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Pneumonia Viral/patologia , Pneumonia Viral/virologia
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