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1.
Zhonghua Er Ke Za Zhi ; 62(3): 204-210, 2024 Mar 02.
Artigo em Chinês | MEDLINE | ID: mdl-38378280

RESUMO

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) (Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS (Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.


Assuntos
Sepse , Humanos , Criança , Masculino , Feminino , Estudos Prospectivos , Estudos Retrospectivos , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Unidades de Terapia Intensiva Pediátrica , Prognóstico , China/epidemiologia , Estado Terminal , Curva ROC , Unidades de Terapia Intensiva
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(11): 1919-1925, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38081610

RESUMO

OBJECTIVE: To investigate the learning curve and clinical efficacy of aortic dissection and non-dissection aortic surgeries through upper hemisternotomy. METHODS: We retrospectively analyzed the perioperative data of aortic dissection and non-dissection surgeries through upper hemisternotomy performed by the same surgical team. Based on cardiopulmonary bypass time and aortic cross-clamping time, the learning curves were plotted using cumulative (CUSUM) analysis and the fitting curve, and the learning process was divided into the improvement period and proficiency period. We compared the perioperative parameters in the two stages, and verified whether the critical point was the number of operations required to overcome the learning curve. The safety and short-term efficacy of the aortic surgeries were analyzed after achieving proficiency. RESULTS: A total of 107 patients were analyzed, including 47 undergoing aortic dissection (ascending aorta replacement + arch replacement + descending aorta stent implantation and/or aortic root treatment) and 60 undergoing non-dissection surgeries (artery root surgery and/or ascending aorta replacement). The optimal fitting equation was y=-0.019x3+0.251x2+28.852x-6.076 (R2=0.918, P < 0.05) for CPB time and y=-0.015x3-0.093x2+34.799x-27.316 (R2=0.92, P < 0.05) for aortic cross-clamping time. In the dissection group, with 27 cases as the boundary, the perioperative parameters were significantly better in the proficiency stage than in the improvement stage, and the critical point was the number of surgeries needed to overcome the learning curve. The best fitting equation was y=0.013x3-1.826x2 + 62.353x+193.189 (R2=0.906, P < 0.05) for CPB time and y= 0.009x3-1.416x2+49.389x+177.335 (R2=0.90, P < 0.05) for aortic cross-clamping time. In the non-dissecting aorta group, where 22 cases served as the boundary, the perioperative parameters were also better in the proficiency period than in the improvement period. CONCLUSION: Both aortic dissection and non-dissection surgeries through upper hemisternotomy are safe and can significantly improve the short-term postoperative efficacy after achieving proficiency, but the latter approach has a shorter learning curve.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Curva de Aprendizado , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Aorta/cirurgia , Resultado do Tratamento , Aneurisma da Aorta Torácica/cirurgia
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(6): 964-969, 2023 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-37439168

RESUMO

OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND). METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1ß, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test. RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1ß, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1ß, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05). CONCLUSION: In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.


Assuntos
Ponte Cardiopulmonar , Microbioma Gastrointestinal , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Interleucina-6 , Fator de Necrose Tumoral alfa , Transtornos Neurocognitivos
4.
Plant Dis ; 107(11): 3602-3607, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37272052

RESUMO

Mucor rot caused by Mucor piriformis is an emerging postharvest disease of mandarin fruit in California. Natamycin is a newly registered biofungicide for postharvest use on citrus and some other fruits. In the study, baseline sensitivity to natamycin in 50 isolates of M. piriformis was determined in vitro. The mean EC50 (effective concentration to inhibit sporangiospore germination by 50%) and MIC (minimum inhibitory concentration to inhibit mycelial growth by 100%) values were 0.59 µg/ml and less than 1.0 µg/ml, respectively. Natamycin at the label rate of 920 µg/ml alone or in combination with 3% potassium sorbate (PS) or 3% sodium carbonate (SC) applied at 20 or 50°C was evaluated for control of Mucor rot on inoculated 'Tango' mandarin fruit. Natamycin alone reduced Mucor rot incidence on stored mandarin fruit from 100% among nontreated control fruit to approximately 30%, a reduction of more than 70% compared to the nontreated control, while 3% PS and 3% SC had no to little control. When applied at 50°C, natamycin and 3% PS reduced Mucor rot incidence by 65.0 and 31.2%, respectively; while natamycin in combination with 3% PS reduced disease incidence by 92.5% compared to the nontreated control after 2 weeks of storage at 5°C. This combined treatment remained effective even when the application of the treatment was delayed for 6 and 12 h after inoculation. However, the effectiveness of the treatments declined when storage was extended to 3 or 4 weeks. Natamycin can be an effective tool to control Mucor rot on mandarin fruit, and minimizing the period of extended storage could help maintain the control efficacy of natamycin.


Assuntos
Frutas , Natamicina , Natamicina/farmacologia , Mucor , Temperatura Alta
5.
Opt Lett ; 48(9): 2433-2436, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126291

RESUMO

Extremely strong terahertz (THz) waves are desperately demanded for investigating nonlinear physics, spectroscopy, and imaging in the THz range. However, traditional crystal-/semiconductor-based THz sources have limitations of reaching extremely high amplitude due to the damage threshold of devices. Here, by introducing Raman amplification to the THz range, we propose a novel, to the best of our knowledge, scheme to amplify THz waves in plasma. A long-pulse CO2 pump laser transfers its energy to a multicycle, 10-THz seed in a two-step plasma. By one-dimensional simulations, a 0.87-GV/m, 1.2-ps-duration THz seed is amplified to 10 GV/m in a 5.7-mm-long plasma with an amplification efficiency approaching 1%. The method provides a new technology to manipulate the intensity of THz waves.

6.
Sci Total Environ ; 888: 164181, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37201849

RESUMO

The concentration of ice nucleating particles (INPs) in the atmosphere is critical for understanding cloud microphysics and predicting the climate system. In this study, we collected surface snow samples along a traverse route from the coastal to the inland of East Antarctica to analyze INP concentrations and identify their spatial variations using a droplet freezing device. The overall concentration of INPs was found to be considerably low along the route, averaging at 0.8 ± 0.8 × 105 L-1 in water and 4.2 ± 4.8 × 10-3 L-1 in air at -20 °C. Although coastal areas had higher levels of sea salt species compared to inland regions, the concentration of INPs remained consistent along the route suggesting less important origination of INPs from the around ocean. Additionally, the heating experiment revealed the important contribution of proteinaceous INPs indicating the presence of biological INPs (bio-INPs). The fraction of bio-INPs was 0.52 on average at -20 °C and ranged from 0.1 to 0.7 from -30 °C to -15 °C. Finally, we parameterize the atmospheric INP concentrations as a function of freezing temperature which can be useful for modeling INP concentrations in this region.

7.
Phys Rev E ; 107(2-2): 025203, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36932603

RESUMO

We have developed a k-space theory for stimulated Raman scattering. The theory is used to calculate the convective gain of stimulated Raman side scattering (SRSS) in order to clarify the discrepancies found between previous gain formulas proposed in the literature. The gains are dramatically modified by the eigenvalue of SRSS, and the maximum gain occurs not at the perfect wave-number matching condition but instead at a wave number having a small deviation that is associated with the eigenvalue. Numerical solutions of the k-space theory equations are compared with, and used to verify, analytically derived gains. We demonstrate connections to the existing path integral theories, and we derive a similar path integral formula in k space.

8.
Osteoarthritis Cartilage ; 31(6): 819-828, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36889626

RESUMO

OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.


Assuntos
Osteoartrite do Joelho , Masculino , Feminino , Humanos , Índice de Massa Corporal , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/genética , Estudo de Associação Genômica Ampla , Causalidade , Articulação do Joelho , Polimorfismo de Nucleotídeo Único
9.
ESMO Open ; 8(2): 101156, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36989884

RESUMO

BACKGROUND: Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in antiangiogenesis which has been an essential strategy for cancer treatment. We report the first-in-human study of AK109, a novel anti-VEGFR2 monoclonal antibody, to characterize the safety profile and pharmacokinetics/pharmacodynamics (PK/PD) properties, and explore the preliminary antitumor efficacy in patients with solid tumors. PATIENTS AND METHODS: This was a multicenter, open-label, phase I study, including dose escalation and dose expansion (NCT04547205). Patients with advanced cancers were treated 2 and 3 weekly with escalating doses of AK109. A 3 + 3 design was used to determine the maximum tolerated dose. Blood was sampled for PK/PD analysis. The primary endpoint was safety and recommended phase II dose (RP2D). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed. However, 38 patients reported treatment-related adverse events (TRAEs); grade ≥3 TRAEs occurred in 10 patients. The most common TRAEs were proteinuria (n = 24, 60%), hypertension (n = 13, 32.5%), increased aspartate transaminase (n = 11, 27.5%), thrombopenia (n = 10, 25%), and anemia (n = 10, 25%). A total of 28 patients (70%) reported adverse events of special interest (AESIs). The most common AESIs were proteinuria (60%), hypertension (32.5%), and hemorrhage (32.5%), mainly including gum bleeding and urethrorrhagia. AK109 exhibited an approximately linear PK exposure with dose escalation at 2-12 mg/kg. PD analyses showed rapid target engagement. Among the 40 patients, 4 achieved partial response and 21 achieved stable disease with an objective response rate of 10% and a disease control rate of 62.5%. Based on the safety profile, the PK/PD profile, and preliminary antitumor activities, 12 mg/kg Q2W and 15 mg/kg Q3W were selected as RP2D. CONCLUSIONS: AK109 showed manageable safety profile and promising antitumor activity, supporting further clinical development in a large population.


Assuntos
Neoplasias , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Neoplasias/patologia
10.
Phys Rev E ; 107(1-2): 015204, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36797903

RESUMO

Higher intensity of strong-coupling stimulated Brillouin scattering (SC-SBS) amplification is achieved by supplementary Raman amplification. In this scheme, a Raman pump laser first amplifies the seed pulse in the homogeneous plasma, and then a SC-SBS pump laser continues the amplification in the inhomogeneous plasma in order to suppress the spontaneous instability of pump lasers. The intensity of the seed laser gets higher and the duration of the seed laser gets shorter than that in the pure SC-SBS scheme with the same incident energy, while the energy conversion efficiency is not significantly reduced. We also found that the SC-SBS amplification is seeded by the leading pulse of Raman amplification. The results obtained from envelope coupling equations, Vlasov simulations, and two-dimensional particle-in-cell simulations agree with each other. This scheme offers a possible way to improve the SC-SBS amplification in experiments.

11.
Rev Sci Instrum ; 93(11): 113501, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36461431

RESUMO

The EAST plasmas heated with deuterium neutral beam injection and ion cyclotron resonance heating (ICRH) have been simulated by the TRANSP code. The analysis has been conducted using the full wave solver TORIC5, the radio frequency (RF)-kick operator, and NUBEAM to model the RF heating effects on fast ion velocity distribution. In this work, we present several simulated results compared with experiments for high power EAST scenarios, indicating that the interactions between ICRH and fast ions can significantly accelerate fast ions, which are confirmed by the increased neutron yield and broadened neutron emission spectrum measurements.

12.
Hum Exp Toxicol ; 41: 9603271221129852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36137816

RESUMO

Lipid metabolism is an important biochemical process in the body. Recent studies have found that environmental endocrine disruptors play an important role in the regulation of lipid metabolism. Bisphenol A (BPA), a common environmental endocrine disruptor, has adverse effects on lipid metabolism, but the mechanism is still unclear. This study aimed to investigate the effects of gestational BPA exposure on hepatic lipid metabolism and its possible mechanism in male offspring. The pregnant Sprague-Dawley rats were exposed to BPA (0, 0.05, 0.5, 5 mg/kg/day) from day 5 to day 19 of gestation to investigate the levels of triglyceride (TG) and total cholesterol (TC), and the expression of liver lipid metabolism-related genes in male offspring rats. The results showed that compared with the control group, the TG and TC levels in serum and liver in BPA-exposed groups was increased. And the expressions of liver fatty acid oxidation related genes, such as peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase 1α (CPT1α), were down-regulated. However, the expressions of fatty acid synthesis related genes, such as sterol regulatory element binding proteins 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1), were up-regulated. The increased protein levels of mTOR and p-CRTC2 suggested that CREB-regulated transcription coactivator 2 (CRTC2) might be an important mediator in the mTOR/SREBP-1 pathway. In conclusion, these results demonstrated that mTOR/CRTC2/SREBP-1 could be affected by gestational BPA exposure, which may involve in the lipid metabolic disorders in later life.


Assuntos
Disruptores Endócrinos , Metabolismo dos Lipídeos , Acetil-CoA Carboxilase/metabolismo , Acetil-CoA Carboxilase/farmacologia , Animais , Compostos Benzidrílicos , Carnitina/farmacologia , Colesterol , Disruptores Endócrinos/toxicidade , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Ácidos Graxos/farmacologia , Feminino , Fígado , Masculino , PPAR alfa/metabolismo , Proliferadores de Peroxissomos/metabolismo , Proliferadores de Peroxissomos/farmacologia , Fenóis , Gravidez , Ratos , Ratos Sprague-Dawley , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Transferases/metabolismo , Transferases/farmacologia , Triglicerídeos
13.
Pharmacol Rev ; 74(3): 462-505, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35710133

RESUMO

The concept of local formation of angiotensin II in the kidney has changed over the last 10-15 years. Local synthesis of angiotensinogen in the proximal tubule has been proposed, combined with prorenin synthesis in the collecting duct. Binding of prorenin via the so-called (pro)renin receptor has been introduced, as well as megalin-mediated uptake of filtered plasma-derived renin-angiotensin system (RAS) components. Moreover, angiotensin metabolites other than angiotensin II [notably angiotensin-(1-7)] exist, and angiotensins exert their effects via three different receptors, of which angiotensin II type 2 and Mas receptors are considered renoprotective, possibly in a sex-specific manner, whereas angiotensin II type 1 (AT1) receptors are believed to be deleterious. Additionally, internalized angiotensin II may stimulate intracellular receptors. Angiotensin-converting enzyme 2 (ACE2) not only generates angiotensin-(1-7) but also acts as coronavirus receptor. Multiple, if not all, cardiovascular diseases involve the kidney RAS, with renal AT1 receptors often being claimed to exert a crucial role. Urinary RAS component levels, depending on filtration, reabsorption, and local release, are believed to reflect renal RAS activity. Finally, both existing drugs (RAS inhibitors, cyclooxygenase inhibitors) and novel drugs (angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors, soluble ACE2) affect renal angiotensin formation, thereby displaying cardiovascular efficacy. Particular in the case of the latter three, an important question is to what degree they induce renoprotection (e.g., in a renal RAS-dependent manner). This review provides a unifying view, explaining not only how kidney angiotensin formation occurs and how it is affected by drugs but also why drugs are renoprotective when altering the renal RAS. SIGNIFICANCE STATEMENT: Angiotensin formation in the kidney is widely accepted but little understood, and multiple, often contrasting concepts have been put forward over the last two decades. This paper offers a unifying view, simultaneously explaining how existing and novel drugs exert renoprotection by interfering with kidney angiotensin formation.


Assuntos
Angiotensinogênio , Doenças Cardiovasculares , Feminino , Humanos , Masculino , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Angiotensinogênio/metabolismo , Doenças Cardiovasculares/metabolismo , Sistemas de Liberação de Medicamentos , Rim/irrigação sanguínea , Rim/metabolismo , Renina/metabolismo , Sistema Renina-Angiotensina , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo
14.
Zhonghua Xue Ye Xue Za Zhi ; 43(4): 293-299, 2022 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-35680627

RESUMO

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.


Assuntos
Sobrecarga de Ferro , Síndromes Mielodisplásicas , Mielofibrose Primária , Ferritinas , Humanos , Ferro , Fígado/metabolismo , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Esplenomegalia
15.
Int J Mol Sci ; 23(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35269547

RESUMO

Contrary to public perception, hypertension remains one of the most important public health problems in the United States, affecting 46% of adults with increased risk for heart attack, stroke, and kidney diseases. The mechanisms underlying poorly controlled hypertension remain incompletely understood. Recent development in the Cre/LoxP approach to study gain or loss of function of a particular gene has significantly helped advance our new insights into the role of proximal tubule angiotensin II (Ang II) and its AT1 (AT1a) receptors in basal blood pressure control and the development of Ang II-induced hypertension. This novel approach has provided us and others with an important tool to generate novel mouse models with proximal tubule-specific loss (deletion) or gain of the function (overexpression). The objective of this invited review article is to review and discuss recent findings using novel genetically modifying proximal tubule-specific mouse models. These new studies have consistently demonstrated that deletion of AT1 (AT1a) receptors or its direct downstream target Na+/H+ exchanger 3 (NHE3) selectively in the proximal tubules of the kidney lowers basal blood pressure, increases the pressure-natriuresis response, and induces natriuretic responses, whereas overexpression of an intracellular Ang II fusion protein or AT1 (AT1a) receptors selectively in the proximal tubules increases proximal tubule Na+ reabsorption, impairs the pressure-natriuresis response, and elevates blood pressure. Furthermore, the development of Ang II-induced hypertension by systemic Ang II infusion or by proximal tubule-specific overexpression of an intracellular Ang II fusion protein was attenuated in mutant mice with proximal tubule-specific deletion of AT1 (AT1a) receptors or NHE3. Thus, these recent studies provide evidence for and new insights into the important roles of intratubular Ang II via AT1 (AT1a) receptors and NHE3 in the proximal tubules in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.


Assuntos
Angiotensina II/metabolismo , Hipertensão/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Angiotensina II/genética , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Mutação com Ganho de Função , Humanos , Hipertensão/genética , Mutação com Perda de Função , Camundongos , Receptor Tipo 1 de Angiotensina/genética , Trocador 3 de Sódio-Hidrogênio/metabolismo
16.
Zhonghua Gan Zang Bing Za Zhi ; 30(2): 207-212, 2022 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-35359073

RESUMO

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.


Assuntos
Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Plaquetas , Humanos , Hipertensão Portal/etiologia , Lipopolissacarídeos , Cirrose Hepática/complicações , Plasma , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Fator A de Crescimento do Endotélio Vascular
17.
Am J Med Qual ; 37(2): 166-172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35230993

RESUMO

Medical errors harm patients and increase costs. Engaging early clinicians in patient safety (PS) is critical but challenging. We evaluated the impact of a Patient Safety Escape Room (PSER) simulation on intern engagement in PS. During the PSER, learner teams identified PS hazards in a simulated hospital room, revealing clues that allow "escape" via event report entry. One-hundred twenty interns from 14 training programs completed 2 PSERs each. Before the PSER, 5% reported experience entering an event report. Following the PSER, all interns had participated in entering an event report. Mean learner-reported comfort in identifying PS hazards improved significantly (6.3 ± 1.57 to 8.0 ± 1.2; P < 0.001). Individual safety hazards were identified by between 6% and 100% of teams. Mean observer-rated teamwork was lower than learner-rated teamwork (41.5 ± 5.18 versus 45.92 ± 3.87; P = 0.01). Subsequent resident reporting rates did not increase compared with historic controls. The PSER engaged early learners, however, translating improvements into the clinical environment remains challenging.


Assuntos
Erros Médicos , Segurança do Paciente , Simulação por Computador , Humanos , Erros Médicos/prevenção & controle
19.
J Emerg Med ; 62(3): 401-412, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35078704

RESUMO

BACKGROUND: Completing an emergency medicine (EM) away rotation is integral to matching successfully into an EM residency program. The demand for EM away rotations (ARs) drives students to submit numerous applications without evidence-based recommendations to guide stakeholders on the approach or number to submit. OBJECTIVES: We conducted a survey study of EM-bound fourth-year medical students to gain insight into their AR application experiences, outcomes, and perceptions. METHODS: We distributed a 40-item questionnaire to EM applicants in Fall 2018 via e-mail through the Clerkship Directors in Emergency Medicine, Council of Residency Directors in EM, and Emergency Medicine Residents' Association listservs. Responses were evaluated using quantitative and qualitative analysis. Primary outcomes were the number of AR applications submitted and AR offers received by students. Secondary outcomes were students' self-assessment of their competitiveness, differences in AR application numbers by degree type, sources of student advising, and student perceptions of the AR application process. RESULTS: There were 253 respondents, consisting of 192 allopathic (MD) and 61 osteopathic (DO) medical students, who met the inclusion criteria, representing about 10% of the applicant pool. On average, students submitted 13.97 applications (95% confidence interval [CI] 11.59-16.35), received 3.25 offers (95% CI 3.01-3.49), and accepted 2.22 offers (95% CI 2.08-2.36). DO candidates submitted twice as many applications as MD candidates while experiencing a similar rate of offers received. Peer influence (n = 154, 61%), peer online advising networks (n = 83, 33%), and self-assessment (n = 114, 45%) were the most often reported causes of increased applications; cost (n = 104, 41%) and geographic limitations (n = 114, 45%) were the most often reported causes of decreased applications. Open-response analysis revealed frustration with lack of standardization (n = 44, 29.5%), insufficient transparency on available positions (n = 37, 24.8%), limited communication (n = 30, 20.1%), and cost (n = 12, 8.1%). CONCLUSIONS: This study showed that, as a whole, students received one away rotation offer for every four to five applications submitted. It clarified factors contributing to increased EM away rotation application submissions and associated stressors inherent in the application experience. Our findings offer insights to inform advising recommendations. They also suggest that stakeholders consider standardizing the process and improve communication over spot availability and application status.


Assuntos
Medicina de Emergência , Internato e Residência , Medicina Osteopática , Estudantes de Medicina , Medicina de Emergência/educação , Humanos , Medicina Osteopática/educação , Inquéritos e Questionários
20.
Rev Sci Instrum ; 92(4): 043552, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243473

RESUMO

Neutron emission spectroscopy and neutron yield measurements are important for high neutral beam injection (NBI) power heating at the Experimental Advanced Superconducting Tokamak (EAST). The neutron yields mainly depend on the deposition from NBI to the deuterium plasmas in the EAST. We have recently used TRANSP with time dependent diagnostic results to simulate the transport process of 30 s long pulse deuterium plasma discharges in the EAST, obtaining the time dependent fast ion distribution, neutron emission spectrum, and total neutron emission rate. Combined with the time trace of the result measured by a standard 235U fission chamber, the effects of different configurations of NBI heating in EAST fusion plasmas have been evaluated.

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