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1.
Bioresour Technol ; 326: 124794, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550210

RESUMO

For solving the challenge in nitrate removal from low C/N wastewater at low temperature, Pseudomonas sp. Y39-6 was isolated and used in nitrate removal. It showed aerobic-heterotrophic denitrification with rate of 1.77 ± 0.31 mg/L·h and unusual aerobic-autotrophic nitrate removal (rate of 0.324 mg/L·h). The aerobic-autotrophic nitrate removal mechanisms were deep investigated by analyzing the nitrate removal process and genomic information. At aerobic-autotrophic condition, the strain Y39-6 could assimilate nitrate to amino acid (NO3- + PHA + CO2 â†’ C5H7O2N) with the carbon source from Polyhydroxyalkanoic acid (PHA) degradation and CO2 fixation. Flagella motivation, swarming activity and extracellular polymeric substances (EPS) production regulated Pseudomonas sp. Y39-6 forming biofilm. Carriers immobilized with Pseudomonas sp. Y39-6 were used in moving bed biofilm reactor (MBBR) and achieved 24.83% nitrate removal at C/N < 1 and 4 °C. Results of this study provided a practical way for nitrogen removal from low C/N wastewater in cold region.


Assuntos
Nitratos , Águas Residuárias , Biofilmes , Reatores Biológicos , Desnitrificação , Nitrogênio , Pseudomonas , Temperatura
2.
Nucleic Acids Res ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591308

RESUMO

The CRISPR/Cas9 system is a technology for genome engineering, which has been applied to indel mutations in genes as well as targeted gene deletion and replacement. Here, we describe paired gRNA deletions along the PIGA locus on the human X chromosome ranging from 17 kb to 2 Mb. We found no compelling linear correlation between deletion size and the deletion efficiency, and there is no substantial impact of topologically associating domains on deletion frequency. Using this precise deletion technique, we have engineered a series of designer deletion cell lines, including one with deletions of two X-chromosomal counterselectable (negative selection) markers, PIGA and HPRT1, and additional cell lines bearing each individual deletion. PIGA encodes a component of the glycosylphosphatidylinositol (GPI) anchor biosynthetic apparatus. The PIGA gene counterselectable marker has unique features, including existing single cell level assays for both function and loss of function of PIGA and the existence of a potent counterselectable agent, proaerolysin, which we use routinely for selection against cells expressing PIGA. These designer cell lines may serve as a general platform with multiple selection markers and may be particularly useful for large scale genome engineering projects such as Genome Project-Write (GP-write).

3.
Eur Urol Oncol ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33436325

RESUMO

BACKGROUND: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes. OBJECTIVE: To precisely estimate the contribution of germline ATM mutations to PrCa risk. DESIGN, SETTING, AND PARTICIPANTS: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated. RESULTS AND LIMITATIONS: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (pdifference = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7). CONCLUSIONS: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families. PATIENT SUMMARY: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier.

4.
Diabetes Care ; 44(2): 499-510, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33355246

RESUMO

OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.

5.
Risk Manag Healthc Policy ; 13: 1965-1975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116977

RESUMO

Background: SARS-CoV-2 infection activates coagulation and stimulates innate immune system. Little is known about coagulopathy and response of inflammation and infection in ICU patients with COVID-19. Derangement of coagulation and markers of infection and inflammation induced by SARS-CoV-2 infection, as well as their correlations were elucidated. Methods: One hundred eight ICU patients with COVID-19 (28 survivors and 80 non-survivors) in Tongji hospital and Wuhan Jinyintan hospital, in Wuhan, China were included. Coagulation parameters, infectious and inflammatory markers were dynamically analysed. The correlation between coagulopathy of patients and infectious and inflammatory markers was verified. Results: SARS-CoV-2-associated coagulopathy occurred in most cases of critical illness. Raised values of d-dimer and FDP were measured in all patients, especially in non-survivors, who had longer PT, APTT, INR, as well as TT, and lower PTA and AT compared to survivors. SIC and DIC mostly occurred in non-survivors. CRP, ESR, serum ferritin, IL-8, and IL-2R increased in all patients, and were much higher in non-survivors who had significantly higher levels of IL-6 and IL-10. D-dimer was positively associated with CRP, serum ferritin (p = 0.02), PCT (p < 0.001), and IL-2R (p = 0.007). SIC scores were positively correlated with CRP (p = 0.006), PCT (p = 0.0007), IL-1ß (p = 0.048), and IL-6 (p = 0.009). DIC scores were positively associated with CRP (p < 0.0001), ESR (p = 0.02), PCT (p < 0.0001), serum ferritin (p < 0.0001), IL-10 (p = 0.02), and IL-2R (p = 0.0005). Conclusion: Prothrombotic state, SIC, and DIC are the characteristics of coagulation in ICU patients with COVID-19. CRP, ESR, serum ferritin, IL-8, IL-2R, IL-6, and PCT were stimulated by SARS-CoV-2 infection. CRP, PCT, serum ferritin, and IL-2R indicate the coagulopathy severity of patients with COVID-19.

6.
Life Sci ; 262: 118506, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33031827

RESUMO

AIMS: Bortezomib (BTZ) is described as the first-line agent for multiple myeloma (MM) chemotherapy, but the emergence of BTZ resistance usually results in the failure of chemotherapy in MM. Circular RNA (circRNA) itchy E3 ubiquitin protein ligase (circITCH) is a novel identified circRNA that plays a vital role in the development of human cancers. However, the role of circITCH in the development of BTZ resistance in MM remains elusive. MATERIALS AND METHODS: The expression of circITCH, miR-615-3p, and protein kinase C, delta (PRKCD) was detected with quantitative reverse transcription PCR and western blot. The effects of circITCH on the sensitivity of MM cells to BTZ were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, flow cytometry, and xenograft tumor assay. The interaction of circITCH, microRNA-615-3p, and PRKCD was explored using luciferase reporter assay and RNA immunoprecipitation assay. KEY FINDINGS: circITCH was downregulated in MM bone marrow specimens and cell lines, as well as BTZ-resistant MM cells. Reduced expression of circITCH was indicative of poor prognosis in MM patients. Upregulation of circITCH enhanced the sensitivity of BTZ-resistant MM cells to BTZ in vitro and in vivo. Furthermore, circITCH was identified as a sponge for miR-615-3p, and PRKCD is confirmed as a direct target of miR-615-3p. Besides, circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis. SIGNIFICANCE: circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis, providing a novel potential target for combating BTZ resistance in patients with MM.

7.
Front Immunol ; 11: 1934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013847

RESUMO

Long non-coding RNA (lncRNA) is pivotal for multiple sclerosis (MS), but the potential mechanism of lncRNA PVT1 in MS animal model, experimental autoimmune encephalomyelitis (EAE) still remains unclear. In this study, macrophages were firstly isolated and induced to polarize into M2 macrophages. M2 macrophage-derived exosomes (M2-exos) were extracted and identified, and EAE mouse model was established and treated with M2-exos. The effect of M2-exos on EAE mice was evaluated by clinical scores. The proportion of Treg and Th17 cells in spinal cord cells and splenocytes, and levels of inflammatory factors were measured. The targeting relationships among PVT1, miR-21-5p, and SOCS5 were verified. The expression of JAKs/STAT3 pathway-related proteins was measured. After M2-exo treatment, the clinical score of EAE mice decreased, and demyelination and inflammatory infiltration improved; Th17 cells decreased, Treg cells increased, and the levels of inflammatory factors decreased significantly. SOCS5 and PVT1 were downregulated and miR-21-5p was upregulated in EAE mice. PVT1 could sponge miR-21-5p to regulate SOCS5. SOCS5 alleviated EAE symptoms by repressing the JAKs/STAT3 pathway. Together, M2-exos-carried lncRNA PVT1 sponged miR-21-5p to upregulate SOCS5 and inactivate the JAKs/STAT3 pathway, thus reducing inflammation and protecting EAE mice. This study may offer novel treatments for MS.

8.
J Ophthalmol ; 2020: 5639284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062313

RESUMO

Purpose: To quantitatively explore the correlation between optical coherence tomography (OCT) parameters and vision impairment in patients with diabetic macular edema (DME). Methods: This study was a retrospective observational case series. One-hundred eyes from 66 patients with DME were retrospectively included. OCT parameters, including central macular thickness (CMT), height of intraretinal cystoid, subretinal fluid and sponge-like retinal swelling, density of hyperreflective foci (HRF), and integrity of the ellipsoidal zone (EZ), were assessed. Correlation analyses and multiple linear regression analysis were performed to quantitatively explore the relationship between best-corrected visual acuity (BCVA) and OCT parameters. Results: Among all OCT parameters, CMT, height of intraretinal cystoid, height of sponge-like retinal swelling, and density of HRF and EZ integrity were significantly correlated with BCVA (r = -0.550, -0.526, -0.411, -0.277, and -0.501, respectively; P < 0.01). In multiple linear regression analysis, CMT, density of HRF, and EZ integrity fit a significant linear equation (ß = 0.482, 0.184, and 0.447, respectively), with the adjusted R square reaching 0.522 (P < 0.001). In eyes without SRF, the height of intraretinal cystoid, density of HRF, and EZ integrity were included in the model and an adjusted R square of 0.605 (P < 0.001) was obtained. Conclusion: In DME eyes, OCT parameters, including the density of HRF, the EZ integrity together with CMT, or the height of intraretinal cystoid, could explain 52.2% to 60.5% of the variation in BCVA and were weighted approximately 2 : 1 : 2, respectively.

9.
BMC Cancer ; 20(1): 856, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894098

RESUMO

BACKGROUND: Germline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging due to biological and technical sources of heterogeneity that vary across the genome within and between samples. METHODS: We developed an approach called CNPBayes to identify latent batch effects in genome-wide association studies involving copy number, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease. RESULTS: Applying a hidden Markov model (HMM) to identify CNVs in a large multi-site Pancreatic Cancer Case Control study (PanC4) of 7598 participants, we found CNV inference was highly sensitive to technical noise that varied appreciably among participants. Applying CNPBayes to this dataset, we found that the major sources of technical variation were linked to sample processing by the centralized laboratory and not the individual study sites. Modeling the latent batch effects at each CNV region hierarchically, we developed probabilistic estimates of copy number that were directly incorporated in a Bayesian regression model for pancreatic cancer risk. Candidate associations aided by this approach include deletions of 8q24 near regulatory elements of the tumor oncogene MYC and of Tumor Suppressor Candidate 3 (TUSC3). CONCLUSIONS: Laboratory effects may not account for the major sources of technical variation in genome-wide association studies. This study provides a robust Bayesian inferential framework for identifying latent batch effects, estimating copy number, and evaluating the role of copy number in heritable diseases.

10.
J Food Biochem ; 44(11): e13461, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32984958

RESUMO

The purple perilla (Perilla frutescens L. Britt.) seed peptides (PPSP) were obtained and their improvement of muscle synthesis and exercise performance was investigated in this work. Results showed that the weight-average molecular weight of the PPSP was 869 Dalton. The PPSP were rich in branched-chain amino acids (18.82 g/100 g) and anti-fatigue amino acids, including glutamate (Glu), aspartic acid (Asp), and arginine (Arg). After the administration of PPSP at 1.2 g kg-1  day-1 for 4 weeks, the muscle coefficient and muscle fiber thickness in mice displayed a distinct (p < .05) increase via the upregulation of myogenic differentiation (MyoD) and myogenin (MyoG). The improved muscle strength and exercise tolerance were also observed. Simultaneously, the levels of the biochemical blood markers associated with fatigue and the glycogen degradation in liver and muscle were significantly (p < .05) suppressed. These results suggested that PPSP could effectively promote muscle synthesis and ameliorate exercise fatigue. PRACTICAL APPLICATIONS: Purple perilla is an annual herbal plant and widely grown in Asian countries as an important crop and food. It is believed that the protein content of purple perilla seeds can reach 23.7%, and the protein is rich in essential amino acids. However, the information about the beneficial effects of their proteins or peptides on muscle synthesis and anti-exercise fatigue were still limited. The present results discovered that the PPSP can effectively promote the growth of muscle tissue and improve exercise tolerance. It is indicated that PPSP may have a potential application value in partly or completely replacing animal proteins such as whey protein.

11.
Hepatology ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931023

RESUMO

BACKGROUND & AIMS: Therapeutic, clinical trial entry and stratification decisions for hepatocellular carcinoma (HCC) are made based on prognostic assessments, using clinical staging systems based on small numbers of empirically selected variables that insufficiently account for differences in biological characteristics of individual patients' disease. APPROACH & RESULTS: We propose a novel approach for constructing risk scores from circulating biomarkers that produce a global biological characterization of individual patient's disease. Plasma samples were collected prospectively from 767 HCC patients and 200 controls, and 317 proteins were quantified in a CLIA-certified biomarker testing laboratory. We constructed a circulating biomarker aberration score for each patient, a score between 0 and 1 measuring the degree of aberration of their biomarker panel relative to normal, that we call HepatoScore. We used log-rank tests to assess its ability to sub-stratify patients within existing staging systems/prognostic factors. To enhance clinical application, we constructed a single-sample score, HepatoScore-14, requiring only a subset of 14 representative proteins encompassing the global biological effects. HCC patients were split into 3 distinct groups with low, medium, and high HepatoScore with vastly different prognoses (mOS 38.2/18.3/7.1m; P<0.0001). Further, HepatoScore accurately sub-stratified patients within levels of existing prognostic factors and staging systems (P<0.0001 for nearly all), providing substantial and sometimes dramatic refinement of expected patient outcomes with strong therapeutic implications. These results were recapitulated by HepatoScore-14, rigorously validated in repeated training/test splits, concordant across Myriad RBM and ELISA kits, and established as an independent prognostic factor. CONCLUSIONS: HepatoScore-14 augments existing HCC staging systems, dramatically refining patient prognostic assessments and therapeutic decision making and enrollment in clinical trials. The novel underlying strategy provides a global biological characterization of disease, and can be applied broadly to other disease settings and biological media.

12.
Mar Drugs ; 18(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751049

RESUMO

Seaweed sulfated polysaccharides have attracted significant attention due to their antibacterial activity. This work investigated the antibacterial activity and mechanism of depolymerized sulfated galactans from Eucheuma serra (E. serra) and Gracilaria verrucosa (G. verrucosa) against enterotoxigenic Escherichia coli (ETEC) K88. The results show that removing the metal ions improves the anti-ETEC K88 activity of the galactans. The fluorescence labeling study confirmed that the sulfated galactans penetrated the cell walls and eventually reached the interior of the ETEC K88. Nucleic acid staining and intracellular protein leakage were also observed, indicating the destruction of permeability and integrity of the cell membrane. Interestingly, the two polysaccharides exhibited no effect on the proliferation of the selected Gram-positive bacteria and yeast. This indicates that the cell wall structure of the microorganisms could influence the bacteriostatic activity of the sulfated polysaccharides, as well. These results suggest that the sulfated seaweed polysaccharides might have potential application value in antibacterial diarrhea.

13.
J Org Chem ; 85(18): 11750-11765, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32808522

RESUMO

To pursue a highly regioselective and efficient reductive Heck reaction, a series of moisture- and air-stable α-diimine palladium precatalysts were rationally designed, readily synthesized, and fully characterized. The relationship between the structures of the palladium complexes and the catalytic properties was investigated. It was revealed that the"bulky-yet-flexible"palladium complexes allowed highly anti-Markovnikov-selective hydroarylation of alkenes with (hetero)aryl bromides under aerobic conditions. Further synthetic application of the present protocol could provide rapid and straightforward access to functional and biologically active molecules.

14.
Genet Epidemiol ; 44(8): 880-892, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32779232

RESUMO

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.

15.
J Sep Sci ; 43(19): 3719-3734, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32725879

RESUMO

An analytical method for the determination of six emerging derivatives or metabolites together with 25 common macrolides antibiotics in milk by ultra-performance liquid chromatography quadrupole/electrostaticfield orbitrap mass spectrometry was established. The samples were purified with optimized Quick, Easy, Cheap, Effective, Rugged, Safe methods. The amounts of primary-secondary amine, C18, and sodium acetate adsorbent materials were optimized by response surface method to obtain the best purification effect. The chromatographic separation was carried out using the XBridge-C18 (2.1 × 100 mm, 3.5 µm, Waters) column with mobile phase of acetonitrile with 0.1% v/v formic acid-water solutions (containing 10 mmol/L ammonium acetate), separated by gradient elution. The instrument was operated in the detection mode of electrospray positive and negative ions with Full MS/data dependent MS2 acquisition mode detection, external standard method was used for quantitative analysis. The limits of detection and limits of quantitation of 31 compounds were 0.1-0.5 µg/L and 0.5-2.0 µg/L, respectively. A total of 31 compounds performed a good linearity in the range of 1 to 200 µg/L, and the correlation coefficient was greater than 0.990. The spiked recoveries in milk samples were 81.07-110.1% and the relative standard deviation was less than 5.1%. The method was successful applied to actual sample testing in the market.

16.
Ther Adv Respir Dis ; 14: 1753466620935770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32600123

RESUMO

EML4-ALK rearranged malignant pleural mesothelioma (MPM) is rare and its responses to anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and lorlatinib, remain unexplored. In this case report, we describe a patient with EML4-ALK-rearranged stage IIIB MPM who was administered with alectinib and lorlatinib as first-line and fourth-line therapy, respectively. He had remarkable response evaluated as partial response on both regimens lasting approximately 3.5 months on each regimen. His plasma samples were collected during the treatment course and submitted for targeted sequencing to understand the molecular mechanisms of his therapeutic resistance. Sequencing analysis revealed the emergence of ALK I1171N and L1196M at alectinib progression. Meanwhile, ALK I1171N, L1196M, and G1202R mutations were identified at lorlatinib progression, wherein L1196M is confirmed to be in cis to G1202R. We speculate that these multiple mutations synergistically mediated his resistance to both alectinib and lorlatinib. Our report describes the detection of EML4-ALK rearrangement in a patient with MPM who had remarkable therapeutic response with ALK inhibitors. Moreover, our case also revealed acquired mechanisms of lorlatinib resistance mediated by multiple mutations ALK I1171N, L1196M, and G1202R, contributing an incremental step to our understanding of the complexity of acquired resistance mechanisms in sequential ALK inhibitor therapy. The reviews of this paper are available via the supplemental material section.

17.
Crit Care Med ; 48(8): e657-e665, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32697506

RESUMO

OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942-0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808-0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784-0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.


Assuntos
Causas de Morte , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Mortalidade Hospitalar , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/mortalidade , APACHE , Adulto , Idoso , Causalidade , China/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Urbanos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/terapia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/terapia , Sobreviventes/estatística & dados numéricos
18.
Diabetes Care ; 43(8): 1902-1909, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32499384

RESUMO

OBJECTIVE: We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. RESEARCH DESIGN AND METHODS: This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. RESULTS: During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs. CONCLUSIONS: The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.

19.
J Med Genet ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546565

RESUMO

PURPOSE: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. METHODS: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. RESULTS: The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. CONCLUSIONS: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32553907

RESUMO

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is a major global health threat. We aimed to describe the characteristics of liver function in patients with SARS-CoV-2 and chronic hepatitis B virus (HBV) co-infection. METHODS: We enrolled all adult patients with SARS-CoV-2 and chronic HBV co-infection admitted to Tongji Hospital from February 1 to February 29, 2020. Data of demographic, clinical characteristics, laboratory tests, treatments, and clinical outcomes were collected. The characteristics of liver function and its relation with the severity and prognosis of disease were described. RESULTS: Of 105 SARS-CoV-2 and chronic HBV co-infected patients, elevated levels of liver test were seen in several patients at admission, including elevated levels of alanine aminotransferase (22, 20.95%), aspartate aminotransferase (29, 27.62%), total bilirubin (7, 6.67%), gamma-glutamyl transferase (7, 6.67%), and alkaline phosphatase (1, 0.95%). The values of the indices mentioned above increased substantially during hospitalization (all P < .05). Fourteen (13.33%) patients developed liver injury. Most of them (10, 71.43%) recovered after 8 (range 6-21) days. Notably, 4 (28.57%) patients rapidly progressed to acute-on-chronic liver failure. The proportion of severe COVID-19 was higher in patients with liver injury (P = .042). Complications including ACLF, acute cardiac injury and shock happened more frequently in patients with liver injury (all P < .05). The mortality was higher in individuals with liver injury (28.57% vs 3.30%, P = .004). CONCLUSION: Liver injury in patients with SARS-CoV-2 and chronic HBV co-infection was associated with severity and poor prognosis of disease. During the treatment of COVID-19 in chronic HBV-infected patients, liver function should be taken seriously and evaluated frequently.

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