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1.
Ying Yong Sheng Tai Xue Bao ; 32(2): 737-749, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650384

RESUMO

The value realization of agro-ecological products is of great significance to China's food security, ecological protection, and strategic blueprint. We reviewed the concepts and boundaries of agricultural ecosystem and agro-ecological products (including agricultural products, other ecosystem services and dis-services). Based on the emergy method, the agricultural ecosystem service quantification method was proposed and the ecosystem services and dis-services of typical agricultu-ral products per unit area in China were calculated. Further, the type-specific values realization pathways of the agro-ecological products were discussed. It was found that 1) the values of the agro-ecological products, which has been realized through market mechanism, can further be added by the means of increasing green degrees or special degree, and establishing agricultural industrial chains; 2) the values of the agro-ecological products, which have not yet been realized through market mechanism, should be compensated or realized through ecological product empowerment and regional shared brand quality commitment; 3) the values of the agro-ecological products can be preserved or increased through reducing the harmfulness of N, P, pesticides and insecticides to ecosystem and human health by multi-approaches-based GHG emission reduction, land nutrient management strategies, and rational landscape architecture; 4) some financial solutions can be promoted, e.g., cancellation of secondary agricultural subsidies, the establishment of ecological trading platform and the certification of ecological products. This study contributes to propose the value realization pathways of agro-ecological products, advance the development of green finance, and promote the modernization of natural resource management capabilities.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Agricultura , China , Ecologia , Humanos
2.
Hepatol Int ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740211

RESUMO

BACKGROUND: Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up. METHODS: A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively. RESULTS: During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012]. CONCLUSION: The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs. CLINICAL TRIALS REGISTRATION: None.

3.
Mol Oncol ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33773029

RESUMO

Aberrant protein acetylation is strongly linked to tumourigenesis, and modulating acetylation through targeting histone deacetylase (HDAC) with small molecule inhibitors has been the focus of clinical trials. However, clinical success on solid tumours, like colorectal cancer (CRC), has been limited, in part because the cancer-relevant mechanisms through which HDAC inhibitors act remain largely unknown. Here, we have explored, at the genome-wide expression level, the effects of a novel HDAC inhibitor CXD101. In human CRC cell lines, a diverse set of differentially expressed genes were up- and down-regulated upon CXD101 treatment. Functional profiling of the expression data highlighted immune-relevant concepts related to antigen processing (AP) and natural killer (NK) cell mediated cytotoxicity. Similar profiles were apparent when gene expression was investigated in murine colon26 CRC cells treated with CXD101. Significantly, these changes were also apparent in syngeneic colon26 tumours growing in vivo. The ability of CXD101 to affect immune-relevant gene expression coincided with changes in the tumour micro-environment (TME), especially in the sub-groups of CD4 and CD8 tumour-infiltrating T lymphocytes. The altered TME reflected enhanced anti-tumour activity when CXD101 was combined with immune checkpoint inhibitors (ICIs), such as anti-PD1 and anti-CTLA4. The ability of CXD101 to re-instate immune-relevant gene expression in the TME and act together with ICIs provides a powerful rationale for exploring the combination therapy in human cancers.

4.
Environ Pollut ; 267: 115631, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254608

RESUMO

Different prediction models have important effects on the accuracy of spatial distribution simulations of heavy metals in soil. This study proposes a model (RFOK) combining a random forest (RF) with ordinary kriging (OK), multi-source environmental data such as terrain elements, site environmental elements, and remote sensing data were incorporated to predict the spatial distribution of heavy arsenic (As) in soil of a certain large arsenic slag site. The predictions results of RFOK were compared with those obtained using the RF, OK, inverse distance weighted (IDW), and stepwise regression (STEPREG) models for assessment of prediction accuracy. The results showed that arsenic pollution was widely distributed and the center of the site, including arsenic slag stacking area and production area were seriously polluted. The overall spatial distribution of arsenic pollution simulated by the five models was similar, but the IDW, RF, OK, and STEPREG showed less spatial variation of soil pollution, while RFOK simulation can better express the characteristics of details in change. The cross-validation results showed that RFOK had the lowest root-mean-square error (RMSE), mean absolute error (MAE), and mean relative error (MRE) relative to the other four models, followed by RF, OK, IDW, and STEPREG. The RMSE, MAE and MRE of RFOK decreased by 62.2%, 64.3% and 68.7%, respectively, relative to the RF model with the second highest accuracy. Compared with the traditional spatial distribution prediction model, the RFOK model proposed in this study has excellent spatial distribution prediction ability for soil heavy metal pollution with large spatial variation characteristics, which can fully explain the nonlinear relationship between pollutant content and its environmental impact elements.

5.
World J Gastroenterol ; 26(46): 7425-7435, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33362394

RESUMO

BACKGROUND: Joint, skin, oral cavity, and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset. The cases of ulcerative colitis with dermatomyositis (DM) are rare. In this study, we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab. CASE SUMMARY: The patient was a 57-year-old female with a 2-year history of DM. The patient was admitted to hospital with abdominal pain, diarrhea, and blood in stool lasting for more than 2 mo. Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum. Pathological sections showed chronic inflammatory cell infiltration, especially neutrophil infiltration, in the colonic mucosa; therefore, the patient was diagnosed with ulcerative colitis. Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM, but its effect was unsatisfactory. The patient's discomfort was relieved after infliximab treatment. CONCLUSION: Infliximab can improve DM in the treatment of ulcerative colitis. Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.

6.
Eur Spine J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180193

RESUMO

BACKGROUND: Posterior atlantoaxial fixation with screw rod forms an approximate "II" shape or "H" increasing transverse link for better stability. In order to improve stability and in consideration of difficult placement of transverse connecting rod, possibility of inadequate bone graft, some scholars have preliminarily researched biomechanics of a novel crossed rod as an approximate "X" configuration of screw rod. PURPOSE: The aim of this study was to evaluate and compare the biomechanics of the crossed and parallel rod configurations in the screw rod system for posterior atlantoaxial fixation on a cadaveric model. METHODS: Six fresh cervical specimens were used to complete the range of motion (ROM) testing by applying pure moments of ± 2.0 nm. Following intact state and under destabilization testing, screws were implanted. The specimens were then tested in the following sequence: Group BLS + PR (C2 bilateral laminar screws + parallel rod), Group BLS + CR (C2 bilateral laminar screws + crossed rod), LPRLS + PR (C2 left pedicle screw and right laminar screw + parallel rod), LPRLS + CR (C2 left pedicle screw and right laminar screw + crossed rod), BPS + PR (C2 bilateral pedicle screws + parallel rod) and BPS + CR (C2 bilateral pedicle screws + crossed rod). The ROM of the C1-2 segments was measured in flexion-extension, lateral bending and axial rotation. Six surgical constructs were compared between the groups and with intact condition, respectively. RESULTS: The six fixed modes significantly increased stability compared with both the intact and destabilization group in flexion-extension, lateral bending and axial rotation (p < .05). In extension, BPS + CR and BLS + CR showed greater stability than BLS + PR (p < .05). During flexion, the six fixation methods showed no statistical significance (p > .05). In left lateral bending, stability of the other five screw rod fixation techniques significantly increased when compared with BLS + PR (p < .05). In the right lateral bending direction, the stability of BLS + PR was worse than that of BPS + CR and BPS + PR (p < .05). In the left axial rotation, stability of BLS + CR, LPRLS + CR and BPS + CR was greater than that of BLS + PR, LPRLS + PR and BPS + PR (p < .05). In the right axial rotation, the stability of BPS + CR and BLS + CR was greater than that of BLS + PR (p < .05). CONCLUSION: The six investigated fixation methods provide sufficient biomechanical stability. The crossed rod configuration can further enhance the axial rotation stability of the screw rod system, which consists of C1 bilateral pedicle and C2 pedicle, or C2 lamina screws. The crossed rod can also improve the stability of the screw rod system made up of C1 bilateral pedicle and C2 lamina screws in lateral bending and extension. The crossed rod configuration is reliable and provides superior stability for clinical application.

7.
J Transl Med ; 18(1): 373, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004038

RESUMO

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes. METHODS: In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. RESULTS: During a median of 37.1 months' follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5 vs. 5.3 vs. 5.6%, p = 0.001) and Fib (4.0 vs. 4.4 vs. 6.1%, p < 0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2 vs. 3.3%, p < 0.001). The highest risk of subsequent CVEs was found in the 9th group (HRadjusted 2.656, 95% CI 1.628-4.333, p < 0.001), which was more significant than Lp(a)-High (HRadjusted 1.786, 95% CI 1.315-2.426, p < 0.001) or Fib-High (HRadjusted 1.558, 95% CI 1.162-2.089, p = 0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013. CONCLUSION: Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.

8.
Curr Med Sci ; 40(5): 879-884, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123903

RESUMO

It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and oxidized low-density lipoprotein (oxLDL) has not been determined. The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein (HDL) as well as oxLDL in untreated patients with coronary atherosclerosis (AS). Thirty-six subjects were enrolled in this study. Of them, 18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls. The plasma lipid profile, lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively. The results showed that pitavastatin treatment indeed not only decreased LDL-C, total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB) levels, and increased HDL cholesterol (HDL-C), but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions. Meanwhile, pitavastatin could decrease plasma oxLDL levels. Furthermore, a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment. We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.

9.
Huan Jing Ke Xue ; 41(10): 4470-4481, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124379

RESUMO

Mobile source emissions have become a major contributor to air pollution in urban areas. Most of the previous studies focus on the emissions from a single source such as on-road mobile source (vehicles) or non-road mobile source (construction machinery, agricultural machinery, ships, railway diesel locomotives, aircraft), but few studies investigate the mobile source emissions as a whole. In this study, we introduced a method for developing mobile source emission inventory with high spatiotemporal resolution, and applied this method in Tianjin in 2017 to analyze the emission compositions and spatiotemporal characteristics there. The results showed that the CO, VOCs, NOx, and PM10 emissions from the mobile sources were 183.03, 64.18, 149.85, and 8.36 thousand tons, respectively. The on-road mobile source was the main contributor to CO and VOCs emissions, accounting for 85.38% and 86.60%, respectively. The non-road mobile source was the main contributor to NOx and PM10 emissions, accounting for 57.32% and 66.95%, respectively. According to the temporal distributions, the mobile source emissions were lowest in February for all pollutants. Moreover, they were highest in October for CO and VOCs and in August for NOx and PM10. Holidays (such as Spring Festival and National Day) have a significant impact on the temporal distribution of the mobile source emissions. According to the spatial distributions, the CO and VOCs emissions were concentrated in urban areas and roads with heavy traffic flow (highways and national highways), and the NOx and PM10 were concentrated in urban areas and port areas. The spatial distributions of different pollutants were determined by the location of their major contributors. This study can provide the required data for fine air pollution control and air quality simulation in Tianjin. Moreover, this method can be applied to the other areas where a mobile source emission inventory needs to be developed.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Agricultura , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Emissões de Veículos/análise
10.
Artigo em Inglês | MEDLINE | ID: mdl-33107573

RESUMO

BACKGROUND: Ultrasound guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. MATERIALS AND METHODS: Data pertaining to 172 patients (38 males and 134 females) who received thermal ablation therapy at 12 hospitals between April 2015 and March 2020 were retrospectively analyzed. The mean duration of follow-up was 24.9 ± 14.1 months (range, 12-60). The technical feasibility, technical success, efficacy, and safety of treatment were analyzed. Post-ablation tumor size at various time-points was compared with pre-ablation measurement. RESULTS: All patients selected for thermal ablation received enlarged ablation according to contrast-enhanced ultrasound post-ablation. The maximum diameter and volume of ablation zone at 6,12, 18, 24, 36, and 48 months post-ablation were significantly smaller than those recorded pre-ablation (P < 0.05 for all). At the most recent follow-up, 106 (61.6%) tumors had completely disappeared. The rate of lymph node metastasis (LNM) was 0.6% (1/172) and the incidence of new tumor was 1.2% (2/172). The overall complication rate was 5.2% (9/172) (major complications: 4.6% [8/172]; minor complications: 0.6% [1/172]). All major complications were relieved within four months post-ablation. CONCLUSION: Thermal ablation may be a feasible, effective, and safe treatment option for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. It may provide a novel treatment option for selected patients.

11.
J Med Internet Res ; 22(10): e22324, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104004

RESUMO

BACKGROUND: Chronic low back pain is a common problem and is associated with high costs, including those related to health care and indirect costs due to absence at work or reduced productivity. Previous studies have demonstrated that acupuncture or electroacupuncture can relieve low back pain. Electronic acupuncture shoes (EAS) are a novel device designed in this study. This device combines the properties of acupuncture and transcutaneous electrical nerve stimulation for clinical use. OBJECTIVE: The aim of this study was to evaluate the efficacy of EAS in patients with chronic low back pain. METHODS: In this prospective double-blinded randomized controlled study, the data of 83 patients who experienced chronic low back pain were analyzed. Patients came to our clinic for 20 visits and underwent assessment and treatment. Patients were randomly allocated to receive either EAS plus placebo nonsteroidal anti-inflammatory drugs (NSAIDs) (EAS group, n=42) or sham EAS plus NSAIDs (NSAID group, n=41). The visual analog scale (VAS) score and range of motion were assessed at baseline, before and after each EAS treatment, and 2 weeks after the last treatment. The time for achieving pain remission was recorded. Quality of life was assessed at the 2nd, 14th, and 20th visits. RESULTS: After 6 weeks of treatment, the treatment success rate in each visit in the EAS group was higher than that in the NSAID group, as revealed by the intention-to-treat (ITT) and per-protocol (PP) analyses, but significant differences were observed only during the 16th visit in the ITT analysis (EAS group: 31/37, 84% and NSAID group: 21/34, 62%; P=.04). The change in the VAS score from baseline in each visit in the EAS group was greater than that in the NSAID group, as revealed by the ITT and PP analyses, and significant differences were observed in the 5th visit and 9th visit in the ITT analysis (P=.048 and P=.048, respectively). Significant differences were observed in the left rotation in the 2nd visit and 4th visit (P=.049 and P=.03, respectively). No significant differences were observed in the VAS score before and after treatment in each visit and in the quality of life in both groups. CONCLUSIONS: EAS might serve as a reliable alternative therapeutic tool for patients with chronic low back pain who are contraindicated for oral NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02468297 https://clinicaltrials.gov/ct2/show/NCT02468297.

12.
Am J Physiol Endocrinol Metab ; 319(6): E1031-E1043, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32954823

RESUMO

Caloric restriction (CR) followed by refeeding, a phenomenon known as catch-up growth (CUG), results in excessive lipid deposition and insulin resistance in skeletal muscle, but the underlying mechanisms remain elusive. Recent reports have suggested that vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation by regulating endothelial fatty acid transport. Here, we found continuous activation of VEGF-B signaling and increased lipid uptake in skeletal muscle from CR to refeeding, as well as increased lipid deposition and impaired insulin sensitivity after refeeding in the skeletal muscle of CUG rodents. Inhibiting VEGF-B signaling reduced fatty acid uptake in and transport across endothelial cells. Knockdown of Vegfb in the tibialis anterior (TA) muscle of CUG mice significantly attenuated muscle lipid accumulation and ameliorated muscle insulin sensitivity by decreasing lipid uptake. Furthermore, we showed that aberrant histone methylation (H3K9me1) and acetylation (H3K14ac and H3K18ac) at the Vegfb promoter might be the main cause of persistent VEGF-B upregulation in skeletal muscle during CUG. Modifying these aberrant loci using their related enzymes [PHD finger protein 2 (PHF2) or E1A binding protein p300 (p300)] could regulate VEGF-B expression in vitro. Collectively, our findings indicate that VEGF-B can promote transendothelial lipid transport and lead to lipid overaccumulation and insulin resistance in skeletal muscle during CUG, which might be mediated by histone methylation and acetylation.

13.
Cardiovasc Diabetol ; 19(1): 152, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981521

RESUMO

BACKGROUND: Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. METHODS: A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. RESULTS: During a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively. CONCLUSIONS: In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32754119

RESUMO

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.


Assuntos
Glicemia/metabolismo , Infecções por Coronavirus/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus/fisiopatologia , Intolerância à Glucose/complicações , Hiperglicemia/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/virologia , Diabetes Mellitus/virologia , Jejum , Feminino , Seguimentos , Intolerância à Glucose/virologia , Mortalidade Hospitalar , Hospitalização , Humanos , Hiperglicemia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
16.
Cardiovasc Diabetol ; 19(1): 104, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631321

RESUMO

BACKGROUND: The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. METHODS: Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. RESULTS: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. . CONCLUSIONS: In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.


Assuntos
Glicemia/metabolismo , Colesterol/sangue , Remanescentes de Quilomícrons/sangue , Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Estado Pré-Diabético/sangue , Idoso , Biomarcadores/sangue , China/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
17.
Angew Chem Int Ed Engl ; 59(43): 19153-19161, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-32602613

RESUMO

Entangled proteins have attracted significant research interest. Herein, we report the first rationally designed lasso proteins, or protein [1]rotaxanes, by using a p53dim-entwined dimer for intramolecular entanglement and a SpyTag-SpyCatcher reaction for side-chain ring closure. The lasso structures were confirmed by proteolytic digestion, mutation, NMR spectrometry, and controlled ligation. Their dynamic properties were probed by experiments such as end-capping, proteolytic digestion, and heating/cooling. As a versatile topological intermediate, a lasso protein could be converted to a rotaxane, a heterocatenane, and a "slide-ring" network. Being entirely genetically encoded, this robust and modular lasso-protein motif is a valuable addition to the topological protein repertoire and a promising candidate for protein-based biomaterials.

18.
J Am Chem Soc ; 142(32): 13846-13855, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32668150

RESUMO

One of the most common reactions of diazo compounds with alkenes is cyclopropanation, which occurs through metal carbene or free carbene intermediates. Alternative functionalization of alkenes with diazo compounds is limited, and a methodology for the addition of the elements of Z-CHR2 (with Z = H or heteroatom, and CHR2 originates from N2═CR2) across a carbon-carbon double bond has not been reported. Here we report a novel reaction of diazo compounds utilizing a radical-mediated addition strategy to achieve difunctionalization of diverse alkenes. Diazo compounds are transformed to carbon radicals with a photocatalyst or an iron catalyst through PCET processes. The carbon radical selectively adds to diverse alkenes, delivering new carbon radical species, and then forms products through hydroalkylation by thiol-assisted hydrogen atom transfer (HAT), or forms azidoalkylation products through an iron catalytic cycle. These two processes are highly complementary, proceed under mild reaction conditions, and show high functional group tolerance. Furthermore, both transformations are successfully performed on a gram-scale, and diverse γ-amino esters, γ-amino alcohols, and complex spirolactams are easily prepared with commercially available reagents. Mechanistic studies reveal the plausible pathways that link the two processes and explain the unique advantages of each.

19.
Hepatology ; 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32567701

RESUMO

BACKGROUND AND AIMS: Endoplasmic reticulum (ER) stress is an adaptive response to excessive ER demand and contributes to the development of numerous diseases, including nonalcoholic fatty liver disease (NAFLD), which is hallmarked by the accumulation of lipid within hepatocytes. However, the underlying mechanisms remain elusive. MicroRNAs (miRNAs) play an indispensable role in various stress responses, but their implications in ER stress have not yet been systemically investigated. In this study, we identify a negative feedback loop consisting of hepatic ER stress and miR-26a in NAFLD pathogenesis. APPROACH AND RESULTS: Combining miRNA dot blot array and quantitative PCR, we find that miR-26a is specifically induced by ER stress in liver cells. This induction of miR-26a is critical for cells to cope with ER stress. In human hepatoma cells and murine primary hepatocytes, overexpression of miR-26a markedly alleviates chemical-induced ER stress, as well as palmitate-triggered ER stress and lipid accumulation. Conversely, deficiency of miR-26a exhibits opposite effects. Mechanistically, miR-26a directly targets the eukaryotic initiation factor 2α, a core ER stress effector controlling cellular translation. Intriguingly, miR-26a is reduced in the livers of patients with NAFLD. Hepatocyte-specific restoration of miR-26a in mice significantly mitigates high-fat diet-induced ER stress and hepatic steatosis. In contrast, deficiency of miR-26a in mice exacerbates high-fat diet-induced ER stress, lipid accumulation, inflammation and hepatic steatosis. CONCLUSIONS: Our findings suggest ER stress-induced miR-26a up-regulation as a regulator for hepatic ER stress resolution, and highlight the ER stress/miR-26a/eukaryotic initiation factor 2α cascade as a promising therapeutic strategy for NAFLD.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32419794

RESUMO

Background: The relationship between inflammatory bowel disease and gut microbiota is inextricable. Electroacupuncture (EA) can alleviate acute experimental colitis, but the performance of intestinal microorganisms and the mechanism are still not fully understood. We investigated the relationship between the EA and gut microbes and clarified the role of tight junction and adiponectin in the anti-inflammatory effect of EA. Methods: Male C57BL/6 mice were randomized into three groups: normal control, dextran sulfate sodium- (DSS-) induced ulcerative colitis (DSS), and DSS with EA ST36 (DSS + EA). Mice body weight, DAI score, colon length, and histological score were evaluated for colitis severity. Colonic inflammation and tight junctions were demonstrated by the immunohistochemical (IHC) method. Systemic responses were confirmed by plasma cytokines and adiponectin with multiplex immunoassays. Gut microbiome profiling was conducted by 16S rRNA gene sequencing. Results: EA had benefit in relieving both macroscopic and microscopic colonic inflammation. It can reduce disease activity, maintain colon length, and ameliorate histological inflammatory reaction. In IHC stain, EA decreased CD11b, F4/80, TLR4, and MyD88 and preserved claudin-1 and ZO-1 expression. Compared with the control group, the DSS group showed elevated levels of CRP, IFN-γ, TNF-α, and IL-6, but decreased adiponectin. These changes were reversed by EA, accompanied by modulation of the overall structure of gut microbiota. Conclusion: Our findings suggest that EA exerts its therapeutic effect by TLR4 signaling via the MyD88-dependent pathway. EA could increase adiponectin, maintain mucosal tight junctions, and modulate gut microbiota.

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