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1.
Cell Rep Med ; 3(3): 100563, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35492878

RESUMO

The hepatic venous pressure gradient (HVPG) is the gold standard for cirrhotic portal hypertension (PHT), but it is invasive and specialized. Alternative non-invasive techniques are needed to assess the hepatic venous pressure gradient (HVPG). Here, we develop an auto-machine-learning CT radiomics HVPG quantitative model (aHVPG), and then we validate the model in internal and external test datasets by the area under the receiver operating characteristic curves (AUCs) for HVPG stages (≥10, ≥12, ≥16, and ≥20 mm Hg) and compare the model with imaging- and serum-based tools. The final aHVPG model achieves AUCs over 0.80 and outperforms other non-invasive tools for assessing HVPG. The model shows performance improvement in identifying the severity of PHT, which may help non-invasive HVPG primary prophylaxis when transjugular HVPG measurements are not available.


Assuntos
Inteligência Artificial , Hipertensão Portal , Diagnóstico por Imagem , Humanos , Hipertensão Portal/diagnóstico por imagem , Cirrose Hepática/complicações , Pressão na Veia Porta
2.
Analyst ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510673

RESUMO

A label-free and ultrasensitive electrochemical biosensor for oral cancer overexpressed 1 (ORAOV1) gene was constructed via exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. Capture DNA with a sulfhydryl group at its 3' terminus was modified onto the surface of a bare gold electrode via an Au-S bond. Assisted DNA hybridized with basal DNA to form hybrid DNA in advance, and ORAOV1 gene hybridized continuously with such a hybrid DNA from the other terminus to construct intact double-stranded DNA. Exonuclease III digested basal DNA in such intact double-stranded DNA specifically, and both ORAOV1 gene and assisted DNA were released into solution. ORAOV1 gene induced another intact double-stranded DNA digestion for target recycling, while assisted DNA hybridized with the capture DNA to form double-stranded DNA on the modified electrode surface. Unhybridized capture DNA on the modified electrode surface was hydrolyzed by RecJf exonuclease to reduce the background electrochemical signal. The 3' terminus of double-stranded DNA on the modified electrode surface was prolongated to be guanine-rich oligonucleotides under the catalysis of terminal deoxynucleotidyl transferase. In the presence of K+ ions, hemin adsorbed onto guanine-rich oligonucleotides to construct a G-quadruplex/hemin complex with a large steric hindrance effect to efficiently avoid the charge transfer of the [Fe(CN)6]3-/4- probe toward the electrode surface. The electrochemical impedance value was increased significantly after the addition of ORAOV1 gene via exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. The electrochemical impedance value was linearly related to the logarithmic concentration of ORAOV1 gene in the range from 0.05 fM to 20 pM, and the detection limit of ORAOV1 gene was low to 0.019 fM. This biosensor was used to detect ORAOV1 gene in complicated human saliva samples with satisfactory results.

3.
Sci Total Environ ; : 155806, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35561898

RESUMO

BACKGROUND: Transportation noise is second only to air pollution as an environmental contributor to adverse health outcomes in Western countries. However, no studies investigated the association between road traffic noise and behavioral problems among schoolchildren in China. OBJECTIVE: To investigate the association between exposure to road traffic noise at home and behavioral problems in Chinese schoolchildren. METHODS: From January to June 2017, we screened 3236 children aged 7-13 years in Guangzhou (Guangdong, China) from the first investigation of an ongoing school-based cohort study with complete information on behavioral problems and residential geolocation. Residential road traffic noise exposure levels were assessed using a validated modeling method in different periods of the day, including daytime (Lday), nighttime (Lnight), and weighted 24-hr (Ldn). The annual mean concentration of nitrogen dioxide was also modeled in our study. Behavioral problems were assessed by the parent-rated Strengths and Difficulties Questionnaire (SDQ). Generalized linear mixed models were utilized to estimate the associations between road traffic noise and behavioral problems. RESULTS: In the main adjusted model, a 10-dB increase in Ldn was associated with 0.33 (95% CI: 0.08, 0.59), 0.08 (95% CI: -0.01, 0.17), and 0.09 (95% CI: 0.01, 0.16) increases in three subscales score for total difficulties score, emotional problems, and conduct problems, respectively. The same increase in Ldn was also associated with the abnormal total difficulties score (OR = 1.25, 95%CI: 1.01, 1.55), emotional problems (OR = 1.19, 95%CI: 0.98, 1.44), and conduct problems (OR = 1.28, 95%CI:1.02, 1.63). Externalising behavior appears more susceptible to traffic noise than internalising behavior. NO2 had a small impact on the associations between Ldn and behavioral problems. Our estimates were generally robust in several sensitivity analyses. CONCLUSION: Residential road traffic noise exposure might be related to increased behavioral problems in Chinese schoolchildren, such as emotional symptoms and conduct problems.

4.
ACS Omega ; 7(17): 14746-14755, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35557690

RESUMO

The dual-porosity model has been used widely to describe the fracture network in well test or numerical simulation due to the high computational efficiency. The shape factor, which can be used to determine the capability of mass transfer between the matrix and fracture, is the core of the dual-porosity model. However, the conventional shape factor, which is usually obtained under pseudo-steady state assumption, has certain limitation in characterization of the mass transfer efficiency in a shale/tight reservoir. In this study, a new transient interporosity flow model has been established by considering the influence of nonlinear flow, stress sensitivity, and fracture pressure depletion. To solve this new model, a finite difference and Newton iteration method was applied. According to the Duhamel principle, the solution for time-dependent fracture pressure boundary condition has been obtained. The solution has been verified by using the fine-grid finite element method. Then, the influence of nonlinear flow, stress sensitivity, and fracture pressure depletion on shape factor and interporosity flow rate has been studied. The study results show that constant shape factors are not suitable for unconventional reservoirs, and the interporosity flow in the shale/tight reservoir is controlled by multiple factors. The new model can be used in test interpretation and numerical simulation, and also provides a new approach for the optimization of the perforation cluster number.

5.
Phys Chem Chem Phys ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537374

RESUMO

The thermoelectric properties of intrinsic n-type ß-Ga2O3 are evaluated by first-principles calculations combined with Boltzmann transport theory and relaxation time approximation. The electron mobility is predicted by considering polar optical phonon scattering in ß-Ga2O3. A temperature power law of T-0.67 is obtained for the intrinsic electron mobility. Due to the ultra-wide band gap of 4.7-4.9 eV, ß-Ga2O3 has a large Seebeck coefficient. As a result, a maximum power factor of 3.1 × 10-3 W m-1 K-2 is obtained at 1600 K. A clear anisotropy in lattice thermal conductivity is observed, with the highest thermal conductivity of 23.1 W m-1 K-1 at 300 K along the [010] direction, and a lower value of 13.2 and 12.2 W m-1 K-1 along the [001] and [100] directions, respectively. A high ZT value of 1.07 at 1600 K can be obtained at the optimal carrier concentration of 2.4 × 1019 cm-3, which is superior to that of most other oxides such as ZnO. In addition, the lattice thermal conductivity can be reduced by precisely adjusting the grain size, and the lattice thermal conductivity at 300 K (1600 K) can be reduced by 73% (39%) when the grain size is decreased to 10 nm. The excellent thermoelectric properties of ß-Ga2O3 have promoted its potential application in the field of high temperature thermoelectric conversion.

6.
Front Oncol ; 12: 754067, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530348

RESUMO

Background: The purpose of our research was to explore the value of preoperative CT and MRI examinations and clinical indicators in the prediction of recurrence of ovarian serous carcinoma in patients who underwent satisfactory staging surgery. Procedure: Detailed inclusion and exclusion criteria were installed to screen all patients collected and the eligible patients were divided into two groups. The CT and MRI features and some clinical characteristics of two groups were analyzed, in addition, the apparent diffusion coefficient (ADC) value in tumor solid region was measured. Univariate analysis was used in this study. Results: There were 78 patients with histologically proven ovarian serous carcinoma. According to the strict inclusion and exclusion criteria, we retained 29 patients (recurrence group: 11 patients, no recurrence group: 18 patients). For the peritoneal implantation metastasis in CT or MRI images and Ki67 proliferation index (Ki67 PI), the differences between two cohorts were statistically significant (P < 0.05). The rate of peritoneal metastasis in the recurrence cohort (10/11, 91%) was higher than that in the no recurrence cohort (7/18, 39%). Patients with high Ki67 PI expression had lower recurrence risk than those with low Ki67 PI expression, HR=0.172 (95%CI: 0.050-0.589, P=0.005), and patients without peritoneal planting had lower recurrence risk than those with it, HR=9.373 (95%CI: 1.194-73.551, P=0.033). For FIGO III patients, ipsilateral fallopian tube involvement was statistically significant between the two groups (P < 0.05). The differences in the other preoperative imaging characteristics of ovarian serous cancer, including the volume; capsule of the mass; main components; ADC value; cystic change; bleeding; degree of enhancement of the mainly solid region in 3 periods; and range of tumor involvement in the ovary, uterus, bladder, bowel, and pelvic wall, were not statistically significant. In addition, the differences in the other clinical indicators (i.e., age, FIGO stage) between the two cohorts were not statistically significant. Conclusions: In CT and MRI examinations before surgery, peritoneal implantation metastasis was suggestive of the possibility of the recurrence of serous ovarian carcinoma in the near future. In addition to that, ipsilateral fallopian tube involvement and Ki67 PI may also indicate the possibility of recurrence (the former was only applicable to FIGO III patients).

7.
Cells ; 11(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563857

RESUMO

Multinucleated retinal pigment epithelium (RPE) cells have been reported in humans and other mammals. Rodents have an extremely high percentage of multinucleated cells (more than 80%). Both mouse and human multinucleated RPE cells exhibit specific regional distributions that are potentially correlated with photoreceptor density. However, detailed investigations of multinucleated RPE in different species and their behavior after DNA damage are missing. Here, we compared the composition of multinucleated RPE cells in nocturnal and diurnal animals that possess distinct rod and cone proportions. We further investigated the reactive oxygen species (ROS) production and DNA damage response in mouse mononucleated and multinucleated RPE cells and determined the effect of p53 dosage on the DNA damage response in these cells. Our results revealed an unrealized association between multinucleated RPE cells and nocturnal vision. In addition, we found multinucleated RPE cells exhibited increased ROS production and DNA damage after X-ray irradiation. Furthermore, haploinsufficiency of p53 led to increased DNA damage frequency after irradiation, and mononucleated RPE cells were more sensitive to a change in p53 dosage. In conclusion, this study provides novel information on in vivo PRE topography and the DNA damage response, which may reflect specific requirements for vision adaption and macular function.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35564813

RESUMO

Home care patients have swallowing dysfunction and rely on an in-dwelling nasogastric tube (NGT) to complement oral food intake, supplement their diet, and maintain adequate nutritional status. This study explored the relationship between aspiration pneumonia (AP) and feeding care among home care patients with an in-dwelling NGT. This preliminary study employed a cross-sectional design. There were 35 patients who relied on an in-dwelling NGT to complement their oral intake of food (NGT-oral feeding) and their primary caregivers participated in this study. All of them developed AP in the past year. Factors involving food intake performance during mealtime of the home care patients and feeding care provided by the caregivers were simultaneously observed and recorded. Among the six risk factors univariately correlated with the incidence of AP, feeding in a noisy environment, using a large spoon to feed the participants, more than 5 mL of food per mouthful, food intake duration lasting > 30 min, swallowing twice for each mouthful of food, and coughing at least once every day remained significant in the logistic regression model (all p < 0.05). Four risk factors for AP were correlated with feeding care; the adjusted risk ratio ranged from 6.17 to 14.96 (all p < 0.05). In addition to each individual's food intake ability, improper feeding assistance was related to the risk factors for AP among home care patients with NGT-oral feeding. Thus, home caregivers should receive safe oral feeding education and training.

9.
Cardiovasc Diabetol ; 21(1): 78, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578337

RESUMO

BACKGROUND: Weight management is strongly promoted for overweight or obese patients with type 2 diabetes (T2DM) by current guidelines. However, the prognostic impact of weight loss achieved without behavioural intervention on the mortality and cardiovascular (CV) outcomes in diabetic patients is still contested. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies that investigated the association of weight loss or weight variability with mortality and CV outcomes. Results of studies that measured weight loss by percentage weight loss from baseline and stratified it as > 10% and 5-10% or studies that computed weight variability were pooled using random effects model. Study quality was evaluated using the Newcastle-Ottawa Scale. RESULTS: Thirty eligible studies were included in the systematic review and 13 of these were included in the meta-analysis. Large weight loss (> 10%) was associated with increased risk of all-cause mortality (pooled hazard ratio (HR) 2.27, 95% CI 1.51-3.42), composite of major CV events (pooled HR 1.71, 95% CI 1.38-2.12) and CV mortality (pooled HR 1.50, 95% CI 1.27-1.76) among T2DM patients. Moderate weight loss showed no significant association with all-cause mortality (pooled HR 1.17, 95% CI 0.97-1.41) or CV outcomes (pooled HR 1.12, 95% CI 0.94-1.33). Weight variability was associated with high hazard of all-cause mortality (pooled HR 1.54, 95% CI 1.52-1.56). CONCLUSIONS: Large weight loss and large fluctuations in weight are potential markers of increased risk of mortality and CV events in T2DM patients. Maintaining a stable weight may have positive impact in these patients.

10.
Eur Radiol ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35471667

RESUMO

OBJECTIVES: We aimed to investigate the additional significance of cerebral small vessel disease (SVD) beyond collaterals in determining the clinical outcome after acute ischemic stroke (AIS). METHODS: We retrospectively reviewed large vessel-involved stroke patients who had baseline CTA within 24 h after symptom onset and had an MRI scan 5 days after admission from October 1, 2018, to October 31, 2021. Collaterals and SVD markers (including atrophy, leukoaraiosis, lacunes, and perivascular space) were graded on CT angiography and MR images, respectively. Modified Rankin Scale (mRS) score at 90 days was recorded, and mRS ≤ 2 was regarded as a good clinical outcome. The associations between SVD markers, collaterals, and mRS were analyzed using logistic and causal mediation regression. RESULTS: We finally enrolled 119 patients (70 ± 13 years). The multivariable regression showed atrophy (evidence: OR 0.05 [95% CI 0.01-0.31], p = 0.002; severe: OR 0.08 [95% CI 0.01-0.44], p = 0.007) and evidence of lacune (OR 0.30 [95% CI 0.08-0.96], p = 0.049) were associated with poor clinical outcomes after correcting covariables. Collaterals mediated 25.74% of the effect of atrophy on poor clinical outcomes (p < 0.001), while lacune impacted clinical outcomes without collaterals' mediation effect (p = 0.54). The classification model with atrophy and lacune had a significantly higher AUC than without markers to distinguish good and poor outcomes (p = 0.036). CONCLUSIONS: Beyond collaterals, brain frailty, specifically assessed by atrophy and lacune, was essential in evaluating stroke patients and could additionally improve the stroke outcome prediction. KEY POINTS: • Beyond collaterals, brain frailty, specifically assessed by brain atrophy and lacune, was still an independent risk factor of unfavorable clinical outcomes after AIS. • Adding brain atrophy and lacune into the model has an extra benefit in predicting stroke outcomes. • The effect of atrophy on stroke outcomes was proportionally mediated through collaterals, but about three-quarters of the effect of brain atrophy and the total effect of lacune directly impacted stroke outcomes without a mediation effect of collaterals.

11.
Curr Med Sci ; 42(2): 280-285, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35438471

RESUMO

OBJECTIVE: Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder PRRT2 gene mutations have been reported to cause PKD. However, the pathophysiological mechanism of PKD remains unclear, and it is unknown whether an inflammatory response is involved in the occurrence of this disease. We aimed to investigate the symptomatology, genotype, and serum cytokines of patients with PKD. METHODS: We recruited 21 patients with PKD, including 7 with familial PKD and 14 with sporadic PKD. Their clinical features were investigated, and blood samples were collected, and PRRT2 mutations and cytokine levels were detected. RESULTS: The mean age at PKD onset was 12.3±2.2 years old. Dystonia was the most common manifestation of dyskinesia, and the limbs were the most commonly affected parts. All attacks were induced by identifiable kinesigenic triggers, and the attack durations were brief (<1 min). Four different mutations from 9 probands were identified in 7 familial cases (71.4%) and 14 sporadic cases (28.6%). Two of these mutations (c.649dupC, c.620_621delAA) had already been reported, while other 2 (c.1018_1019delAA, c.1012+1G>A) were previously undocumented. The tumor necrosis factor (TNF)-α level in the PKD group was significantly higher than that in the age- and sex-matched control group (P=0.025). There were no significant differences in the interleukin (IL)-1ß, IL-2R, IL-6, IL-8, or IL-10 levels between the two groups. CONCLUSION: In this study, we summarized the clinical and genetic characteristics of PKD. We found that the serum TNF-α levels were elevated in patients clinically diagnosed with PKD, suggesting that an inflammatory response is involved in the pathogenesis of PKD.


Assuntos
Distonia , Adolescente , Criança , Citocinas/genética , Distonia/diagnóstico , Distonia/genética , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética
12.
Anal Chem ; 94(17): 6607-6614, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35446026

RESUMO

The dysfunctional islet ß-cell triggered by excessive deposition of Zn2+ constituted a striking indicator of the occurrence of diabetic disease. However, it remained a formidable challenge to reflect the real-time function of ß-cell by monitoring the Zn2+ content. Herein, multistage photoactivatable Zn2+-responsive nanodevice (denoted as AD2@USD1) was presented for sensing, regulating, and evaluating Zn2+ levels in dysfunctional islet ß-cells. The photoactivated signatures on the satellite shell layer of the nanodevices and the internally loaded chelating factors effectively identified and intervened in the real-time concentration of Zn2+, the photothermal feedback component decorated on the inner core permitted the assessment of the post-intervention Zn2+ levels, achieving an integrated intervention and prognostic assessment in response to the abnormal islet ß-cell function induced by Zn2+ deposition. In this way, one strategy for sensing and regulating islet ß-cell function-oriented to Zn2+ was established. Our study introduced AD2@USD1 as a tool for effectively sensing, adjusting, and assessing the Zn2+ level in islet ß-cells with abnormalities, gaining a potential breakthrough in the treatment of diabetes.


Assuntos
Diabetes Mellitus , Células Secretoras de Insulina , Ilhotas Pancreáticas , Quelantes , Humanos , Zinco
13.
Environ Res ; 212(Pt B): 113261, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35413300

RESUMO

Atmospheric amines have attracted increasing attention due to their significant impact on new particle formation, particle hygroscopicity and particle optical properties. In this study, four low-molecule-weight amines were detected from PM2.5 filter samples collected at an urban site of Pearl River Delta (PRD) region of China in 2018 autumn. During the campaign, the mass concentrations of ambient particulate methylamine (MA, CH3NH2), dimethylamine (DMA, (CH3)2NH), trimethylamine (TMA, (CH3)3N), and diethylamine (DEA, (C2H5)2NH) were quantified at daily or 12-h resolution using an optimized Ion Chromatograph (IC) method. The total measured amine concentration was 297 ± 209 ng/m3, which can account for 0.76 ± 0.33% of PM2.5 mass concentrations. The particulate amines in PRD urban area were dominated by MA (243 ± 179 ng/m3), accounting for over 80% of total amines, then followed by DMA (49 ± 30 ng/m3, 16.5%), TMA (4 ± 2 ng/m3) and DEA (1 ± 1 ng/m3). Based on the correlation analysis, MA and DMA mainly presented as nitrate and sulfate salts. We speculate the amines tend to react with gas-phase HNO3 or particle-phase nitrate to form particulate amine salts via local process in Guangzhou. As the relative humidity (RH) increased, enhanced partitioning of amine towards the particle phase was observed. Using approach of multiple linear regression, 71% of the particulate amines in PRD urban site could be explained by acid-base process and the rest by primary emissions from combustion sources (29%).

14.
Can J Gastroenterol Hepatol ; 2022: 7235860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369116

RESUMO

Methods: We identified relevant cohort studies that assessed the relationship between liver fibrosis scores (e.g., FIB-4, NAFLD fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)) and associated prognosis outcomes by searching the PubMed, EMBASE, and medRxiv databases. The potential dose-response effect was performed using a stage robust error meta-regression. Results: Sixteen studies with 8,736 hospitalized patients with COVID-19 were included. One-point score in FIB-4 increase was significantly associated with increased mechanical ventilation (RR: 2.23, 95% CI: 1.37-3.65, P=0.001), severe COVID-19 (RR: 1.82, 95% CI: 1.53-2.16, P < 0.001), and death (RR: 1.47, 95% CI: 1.31-1.65, P < 0.001), rather than hospitalization (RR: 1.35, 95% CI: 0.72-2.56, P=0.35). Furthermore, there is a significant positive linear relationship between FIB-4 and severe COVID-19 (P nonlinearity=0.12) and mortality (P nonlinearity=0.18). Regarding other liver scores, one unit elevation in APRI increased the risk of death by 178% (RR: 2.78, 95% CI: 1.10-6.99, P=0.03). Higher NFS (≥-1.5) and Forns index were associated with increased risk of severe COVID-19 and COVID-19-associated death. Conclusion: Our dose-response meta-analysis suggests high liver fibrosis scores are associated with worse prognosis in patients with COVID-19. For patients with COVID-19 at admission, especially for those with coexisting chronic liver diseases, assessment of liver fibrosis scores might be useful for identifying high risk of developing severe COVID-19 cases and worse outcomes.


Assuntos
COVID-19 , Hepatopatia Gordurosa não Alcoólica , COVID-19/epidemiologia , Hospitalização , Humanos , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Respiração Artificial/efeitos adversos
15.
Inquiry ; 59: 469580221096257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35475411

RESUMO

Objective: Explore the distribution of basic characteristics of high-risk groups of diabetes; verify the practical significance and diagnostic value of the "three-point method"; layered analysis of glycated hemoglobin and glycated serum albumin, and study its value and significance in the diagnosis of diabetes mellitus, Type II and pre-diabetes mellitus, Type II.Methods: 1304 high-risk individuals with T2D in Shanghai, 529 males and 841 females with an average of (50.5 ± 15.2) years old, were examined by oral glucose tolerance test (OGTT), HbA1c and GA were determined. Process the data by Python and GraphPad; judge the diagnostic value of HbA1C, GA by ROC.Results: (1) The numbers of DM, NGT, HOG, IFG, Mild-IGT and Mid-IGT in the objects were 647, 141, 70, 4, 208 and 234 respectively. In the 43-49 age group with a higher incidence, the proportion of selected high-risk groups is low. (2) The sensitivity and specificity about "three-point method" used to determine NGT is 100% and 90.11%; to determine IGR is 75.11% and 97.32%; to determine HOG is 97.14% and 100%; to determine DM is 94.67% and 100%. (3) According to ROC judgment, it is found that these 2 did not have the function of separate diagnoses, the optimal critical point of HbA1C related to DM status is 5.95%, (P<.01); HbA1C related to IGR status is 5.75% (P<.01); of GA related to DM status is 15.25% (P<.01); GA related to IGR status is 14.95% (P<.01).


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Idoso , China , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Glucose , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Anal Methods Chem ; 2022: 5914581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433070

RESUMO

A high-performance liquid chromatographic method coupled with triple quadrupole mass spectrometry (LC-MS/MS) for the analysis of blonanserin and its active metabolite, N-desethyl blonanserin, in rat plasma has been developed and validated. The biological samples were treated by simple direct protein precipitation before separation on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with a column temperature of 35°C at a flow rate of 0.5 mL/min. The mobile phase A is a mixture of methanol and water (75 : 25, v/v, 5 mM ammonium formate), and the mobile phase B is acetonitrile containing 0.1% formic acid. The ratio of mobile phase A to mobile phase B is 15 : 85. Electrospray ionization (ESI) multiple reaction monitoring modes are used for detection, which are m/z 368.10 ⟶ 296.90 (blonanserin), m/z 340.15 ⟶ 297.05(N-desethyl blonanserin), and m/z 348.15⟶ 302.05 (N-desethyl blonanserin-d8). The linear response range was 0.1-100.0 ng/mL for blonanserin and N-desethyl blonanserin. The lower limit of quantification (LLOQ), calibration curves, carryover, and matrix effects were sufficiently accurate and precise according to the National Medical Products Administration (NMPA) guidelines for bioanalytical method validation. This analytical method was successfully applied in a blonanserin-poloxamer thermosensitive gel pharmacokinetic study in rats.

17.
Front Cardiovasc Med ; 9: 865036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463784

RESUMO

Background: Conflicting findings of the association between serum uric acid (SUA) and atrial fibrillation (AF) have been reported in both men and women. The sex-specific associations between SUA and the risk of AF are unclear, although hyperuricemia is independently associated with the risk of AF. We performed this meta-analysis to assess the sex-specific effect of SUA on the risk of AF. Methods: The PubMed, EMBASE, and Cochrane Library databases were searched up to October 3, 2021, for studies that reported sex-specific associations of SUA levels with AF. Linear relationships were assessed by the generalized least squares trend estimation. This study was registered with PROSPERO (42020193013). Results: Ten eligible studies with 814,804 participants (415,779 men and 399,025 women) were identified. In the category analysis, high SUA was associated with an increased risk of AF in both men (OR: 1.42; 95% CI, 1.18-1.71, I2 = 34%) and women (OR: 2.02; 95% CI, 1.29-3.16, I2 = 70%). In the dose-response analysis, for each 60 µmol/L (1 mg/dL) increase in the SUA level, the risk of AF increased by 15% (OR: 1.15; 95% CI, 1.07-1.25, I2 = 74%) in men and 35% (OR: 1.35; 95% CI, 1.18-1.53, I2 = 73%) in women. There was a borderline difference in the impact of SUA on the risk of AF between men and women (P for interaction = 0.05). A significant linear relationship between SUA and the risk of AF was observed in men (P for non-linearity = 0.91) and women (P for non-linearity = 0.92). Conclusions: This study suggested that there was a significant linear relationship between SUA and the risk of AF among men and women, with a higher risk estimate for women. Additional trials are required to assess the effect of reduced SUA therapy on AF incidence. Systematic Review Registration: https:www.crd.york.ac.uk/PROSPERO/, identifier: CRD 42020193013.

18.
J Immunol Res ; 2022: 5665964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478937

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and the patients are generally diagnosed with distant metastasis. Liver is one of the preferred organs of distant metastasis, and liver metastasis is the leading cause of death in PDAC. Diet-induced obesity (DIO) is a risk factor for PDAC, and it remains unclear whether and how DIO contributes to liver metastasis of PDAC. In our study, we found that DIO significantly promoted PDAC liver metastasis compared with normal diet (ND) in intrasplenic injection mouse model. RNA-seq analysis for liver metastasis nodules showed that the various chemokines and several chemokine receptors were altered between ND and DIO samples. The expression levels of CX3CL1 and CX3CR1 were significantly upregulated in DIO-induced liver metastasis of PDAC compared to ND. Increased CX3CL1 promoted the recruitment of CX3CR1-expressing pancreatic tumor cells. Taken together, our data demonstrated that DIO promoted PDAC liver metastasis via CX3CL1/CX3CR1 axis.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Animais , Receptor 1 de Quimiocina CX3C , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Quimiocina CX3CL1/genética , Dieta , Humanos , Neoplasias Hepáticas/secundário , Camundongos , Obesidade , Neoplasias Pancreáticas/patologia
19.
Environ Sci Technol ; 56(8): 4871-4881, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35369697

RESUMO

Global warming is expected to affect methane (CH4) emissions from rice paddies, one of the largest human-induced sources of this potent greenhouse gas. However, the large variability in warming impacts on CH4 emissions makes it difficult to extrapolate the experimental results over large regions. Here, we show, through meta-analysis and multi-site warming experiments using the free air temperature increase facility, that warming stimulates CH4 emissions most strongly at background air temperatures during the flooded stage of ∼26 °C, with smaller responses of CH4 emissions to warming at lower and higher temperatures. This pattern can be explained by divergent warming responses of plant growth, methanogens, and methanotrophs. The effects of warming on rice biomass decreased with the background air temperature. Warming increased the abundance of methanogens more strongly at the medium air temperature site than the low and high air temperature sites. In contrast, the effects of warming on the abundance of methanotrophs were similar across the three temperature sites. We estimate that 1 °C warming will increase CH4 emissions from paddies in China by 12.6%─substantially higher than the estimates obtained from leading ecosystem models. Our findings challenge model assumptions and suggest that the estimates of future paddy CH4 emissions need to consider both plant and microbial responses to warming.


Assuntos
Euryarchaeota , Oryza , Agricultura , China , Ecossistema , Metano/análise , Óxido Nitroso/análise , Solo , Temperatura
20.
J Neurol ; 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366689

RESUMO

A genetic diagnosis cannot be made in a considerable proportion of patients with hereditary lower motor neuron (LMN) syndromes. The GGC repeat expansion in the 5'untranslated region (5'UTR) of NOTCH2NLC gene has been reported to be associated with a group of NOTCH2NLC-related repeat expansion disorders (NRED), including amyotrophic lateral sclerosis (ALS). The relationship between the mutation and LMN syndromes has not been reported previously. Here, we identified the GGC repeat expansions of NOTCH2NLC in a Chinese familial patient with LMN syndrome, presenting with slowly progressive weakness of four limbs. Needle electromyography revealed evidence of acute denervation and chronic neurogenic changes. Cognition and brain MRI were normal. Initial whole-exome sequencing by next generation sequencing revealed negative results. However, repeat-primed polymerase chain reaction performed on the proband showed a pathogenic GGC expansion in the 5'UTR of NOTCH2NLC and long-read sequencing subsequently revealed 248 GGC repeats. The mutation was co-segregated with the clinical phenotype in the family. Immunofluorescent studies identified p62-positive protein deposits in the intranuclear inclusions in myofibers. The GGC repeat expansion in NOTCH2NLC is associated with a new phenotype of hereditary LMN syndrome. As a result, NOTCH2NLC genotyping should be performed in patients with hereditary LMN syndromes.

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