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Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.
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Agricultura/métodos , Conservação dos Recursos Naturais , Produtos Agrícolas/crescimento & desenvolvimento , Eficiência Organizacional , Fazendeiros , China , Técnicas de Apoio para a Decisão , Grão Comestível/crescimento & desenvolvimento , Política Ambiental , Fertilizantes/estatística & dados numéricos , Abastecimento de Alimentos/métodos , Efeito Estufa , Nitrogênio/metabolismo , Oryza/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Zea mays/crescimento & desenvolvimentoRESUMO
BACKGROUND: To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice. METHODS: OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates. DISCUSSION: The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety. CLINICAL TRIAL REGISTRATION: ClinicalTrial.org Identifier NCT05640752.
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Doença da Artéria Coronariana , Coração , Humanos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Pacientes , Angiografia por Tomografia Computadorizada , Síndrome , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: The aims of this study were to investigate the current status and the influence factors of exercise, and to explore the impact of exercise on the quality of life (QoL) in peritoneal dialysis (PD) patients in the post-COVID-19 period. MATERIALS AND METHODS: Those PD patients who were followed up between September 2020 and August 2021 were enrolled. The collected data included demographic information, clinical data, exercise data, and QoL. RESULTS: In total, 339 PD patients were included in this cross-sectional study. The mean age was 44.0 ± 13.0 years, with a median PD duration of 6.7 (1.7 - 41.9) months. The primary renal disease was glomerulonephritis (68.4%). 277 (81.7%) PD patients performed exercise, with median exercise time 5.0 (3.5 - 7.8) hours per week. The main type of exercise was slow walking. Pain (odds ratio (OR) = 0.311, p = 0.002) and lower hemoglobin level (OR = 1.016, p = 0.033) were independent risk factors for exercise. Moreover, male sex (B = 2.803, p < 0.001) was an independent protective factor, while advanced age (B = -0.097, p < 0.001), higher body mass index (B = -0.154, p < 0.001), and pain (B = -0.643, p = 0.023) were independent risk factors for exercise intensity. After adjustment for other confounders, exercise (B = 5.787, p = 0.037) was an independent protective factor for total score of QoL in PD patients. CONCLUSION: In the current study, 81.7% of PD patients performed exercise in the post-COVID-19 period. Pain and anemia were independent risk factors for exercise in PD patients. Advanced age, female sex, higher body mass index, and pain were independently associated with lower exercise capacity in PD patients. PD patients undergoing exercise had better QoL.
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COVID-19 , Exercício Físico , Falência Renal Crônica , Diálise Peritoneal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/complicações , Estudos Transversais , Falência Renal Crônica/complicações , Dor/complicações , Diálise Peritoneal/efeitos adversos , Qualidade de VidaRESUMO
Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) results in chronic interstitial nephritis, which gradually develops into end-stage renal disease. It is believed that the accumulation of mutant uromodulin causes the endoplasmic reticulum (ER) stress, then leads to the kidney damage. But the underlying mechanism remains unclear. To find the ADTKD-UMOD patients, UMOD gene screening was performed in 26 patients with unexplained chronic interstitial nephritis, during the past 10 years in our department, and among them three ADTKD-UMOD cases were discovered. Routine pathological staining and electron microscopy sections were reviewed again to confirm their kidney lesions. Immunostaining of UMOD and ER stress marker GRP78, as well as CHOP have all been done. The strong colocalization of UMOD with GRP78 and CHOP in ADTKD-UMOD patients but not in other chronic interstitial nephritis patients had been found. Moreover in vitro experiments, ER stress induced by tunicamycin (TM) not only significantly increased the expression of GRP78 and CHOP, but also caused the epithelial to myofibroblast transformation (EMT) of renal tubular epithelial cells, evidenced by decreased expression of E-cadherin and increased expression of vimentin, and extracellular matrix (ECM) deposition, evidenced by increased expression of fibronectin (FN). CHOP knockdown could restore the upregulation of vimentin and FN induced by TM. Thus, specific activation of CHOP in renal tubular epithelial cells induced by UMOD protein might be the key reason of renal interstitial fibrosis in ADTKD-UMOD patients.
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Transição Epitelial-Mesenquimal/genética , Nefrite Intersticial/genética , Fator de Transcrição CHOP/metabolismo , Regulação para Cima/genética , Uromodulina/genética , Adulto , Estresse do Retículo Endoplasmático/genética , Feminino , Humanos , Masculino , Mutação , Adulto JovemRESUMO
Based on thieno[2,3-b]quinoline-2-carbohydrazide and salicylaldehyde, a novel fluorescent probe (L) was designed and synthesized. L could be used as a multifunctional sensor to sequentially detect In3+ and Fe3+ through fluorescence enhancement and fluorescence quenching in DMF/H2 O buffer solutions. At the same time, L had good anti-interference ability, which could still detect In3+ and Fe3+ well in the presence of other metal ions. For F- , it could be detected by enhancing the fluorescence change caused by the introduction of Al3+ . When other anions were present, the detection of F- would not be interfered. The detection limits of In3+ , Fe3+ and F- were 1.16 × 10-10 M, 2.03 × 10-8 M and 7.98 × 10-9 M, respectively. The complexation model and sensing mechanism between L and In3+ , Fe3+ and F- were confirmed by calculating structural optimization and energy optimization using Gaussian 09 software.
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Corantes Fluorescentes , Quinolinas , Ânions , Íons , Espectrometria de FluorescênciaRESUMO
Limited research exists on identifying risk factors for preeclampsia (PE) in the chronic kidney disease (CKD) population, especially across different patient sources. This study aimed to address this gap by analyzing clinical data from CKD pregnant women admitted to Peking University Third Hospital from January 2012 to December 2022. Logistic regression analysis identified independent risk factors for PE in the CKD population and assessed variations among patients from different sources. Additionally, a predictive model for PE was established using data from the registered group. The study included 524 CKD patients. Hypertension, proteinuria, fibrinogen >4 g/L, serum albumin ≤30 g/L, and uric acid >260 µmol/L were independent risk factors for PE in the overall CKD population. Subgroup analysis revealed that hypertension, serum albumin ≤30 g/L, and uric acid >260 µmol/L were independent risk factors in the referred group, while hypertension, uric acid >260 µmol/L, and fibrinogen >4 g/L were independent risk factors in the registered group. The prediction model based on registered group risk factors showed good predictive efficiency, with the area under the curve of 0.774 in the training set and 0.714 in the validation set. In conclusion, this study revealed that hypertension and elevated uric acid are independent risk factors for PE in CKD patients regardless of patient source, while serum albumin and fibrinogen levels are associated with PE risk in specific patient subgroups. Our predictive model enables clinicians to quickly identify the risk of PE in CKD patients, and early intervention treatment to improve pregnancy outcomes.
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Pré-Eclâmpsia , Insuficiência Renal Crônica , Ácido Úrico , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Adulto , Ácido Úrico/sangue , Hipertensão/complicações , Hipertensão/epidemiologia , Fibrinogênio/análise , Fibrinogênio/metabolismo , Albumina Sérica/análise , Proteinúria , Adulto JovemRESUMO
Two new Schiff bases, TIC ((E)-N'-(2-hydroxybenzylidene)-5-(thiophene-2-yl)isoxazole-3-carbohydrazide) and TIE ((E)-N'-(3-ethoxy-2-hydroxybenzylidene)-5-(thiophene-2-yl)isoxazole-3-carbohydrazide), have been designed and synthesized as chemosensors for distinct recognition of Ga3+ and Fe3+ ions. TIE demonstrated a prominent "turn on" response characterized by clear distinguished fluorescence when coordination with Ga3+ ions in the DMSO/H2O buffer solution. In comparison, TIC also showed "turn on" response of blue fluorescence which was more selective and sensitive than that of TIE due to the steric hindrance of ethoxy group of TIE. The newly formed complexes TIC-Ga3+ and TIE-Ga3+ may act as selective "turn-off" fluorescent probes towards Fe3+ ions. Limits of detection of TIC and TIE towards Ga3+ ions were 7.8809 × 10-9 M and 2.6277 × 10-8 M, respectively. Limits of detection of TIC-Ga3+ and TIE-Ga3+ towards Fe3+ ions were 8.6562 × 10-9 M and 3.3764 × 10-7 M, respectively. The molar ratio of the complex between the sensor and Ga3+ or Fe3+ ions were all 1:2 determined through Job's Plot, mass spectrometry, and theoretical calculations. Both sensors were utilized for the determination of target ions in environment water samples, and the portable paper sensors for detecting Ga3+ ions have been successfully developed.
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Previous studies have shown that the C-C motif chemokine ligand 2 (CCL2) is widely expressed in the nervous system and involved in regulating the development of chronic pain and related anxiety-like behaviors, but its precise mechanism is still unclear. This paper provides an in-depth examination of the involvement of CCL2-CCR2 signaling in the anterior cingulate cortex (ACC) in intraplantar injection of complete Freund's adjuvant (CFA) leading to inflammatory pain and its concomitant anxiety-like behaviors by modulation of glutamatergic N-methyl-D-aspartate receptor (NMDAR). Our findings suggest that local bilateral injection of CCR2 antagonist in the ACC inhibits CFA-induced inflammatory pain and anxiety-like behavior. Meanwhile, the expression of CCR2 and CCL2 was significantly increased in ACC after 14 days of intraplantar injection of CFA, and CCR2 was mainly expressed in excitatory neurons. Whole-cell patch-clamp recordings showed that the CCR2 inhibitor RS504393 reduced the frequency of miniature excitatory postsynaptic currents (mEPSC) in ACC, and CCL2 was involved in the regulation of NMDAR-induced current in ACC neurons in the pathological state. In addition, local injection of the NR2B inhibitor of NMDAR subunits, Ro 25-6981, attenuated the effects of CCL2-induced hyperalgesia and anxiety-like behavior in the ACC. In summary, CCL2 acts on CCR2 in ACC excitatory neurons and participates in the regulation of CFA-induced pain and related anxiety-like behaviors through upregulation of NR2B. CCR2 in the ACC neuron may be a potential target for the treatment of chronic inflammatory pain and pain-related anxiety.
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Ansiedade , Quimiocina CCL2 , Giro do Cíngulo , Inflamação , N-Metilaspartato , Dor , Receptores CCR2 , Receptores de N-Metil-D-Aspartato , Transdução de Sinais , Animais , Giro do Cíngulo/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Inflamação/patologia , Inflamação/metabolismo , Masculino , Ansiedade/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Quimiocina CCL2/metabolismo , Receptores CCR2/metabolismo , Receptores CCR2/antagonistas & inibidores , Dor/metabolismo , Dor/patologia , Transdução de Sinais/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Adjuvante de Freund/toxicidade , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Comportamento Animal , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Compostos de Espiro , BenzoxazinasRESUMO
OBJECTIVE: This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction-related pregnancy outcomes in people with autoimmune abnormalities was also explored. METHODS: â To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. â¡ To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed. RESULTS: â There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. â¡ In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ⢠Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population. CONCLUSION: Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population. Key Points â¢The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. â¢Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA. â¢HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement. â¢Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications.
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Síndrome Antifosfolipídica , Antirreumáticos , Lúpus Eritematoso Sistêmico , Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Hidroxicloroquina/uso terapêutico , Antirreumáticos/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Placenta , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado da Gravidez , AutoanticorposRESUMO
Background: Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients. Methods: The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes. Results: (i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p < 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p < 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups. Conclusion: ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.
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OBJECTIVE: Recurrent pregnancy loss (RPL) and pre-eclampsia (PE) are immune-related pregnancy complications that have been linked to CD4+ T cells and their cytokines, which can be influenced by genetic polymorphisms. This meta-analysis aimed to investigate the relationship between interleukin (IL)-17 and -27 polymorphisms and the susceptibility to RPL and PE. METHODS: All eligible case-control studies published up to February 2023 were identified by searching PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar. The risk of recurrent pregnancy loss and PE associated with the IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were estimated for each study. RESULTS: The meta-analysis incorporated a total of 13 studies. The overall analysis indicated that IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with immune-related pregnancy complications, including RPL and PE. However, when the analysis was stratified by disease type, the IL-17 rs2275913 polymorphism was found to be associated with an increased risk of RPL (recessive model AA/GA + GG: OR = 1.68, 95% confidence interval [CI]: 1.13-2.49, p = .01). CONCLUSIONS: The IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with RPL and PE, whereas the IL-17 rs2275913 polymorphism was associated with the susceptibility to recurrent miscarriage.
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Aborto Habitual , Interleucina-27 , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Aborto Habitual/genética , Interleucina-17/genética , Interleucina-27/genética , Interleucinas/genética , Polimorfismo Genético , Pré-Eclâmpsia/genéticaRESUMO
A new Schiff base sensor (E)-N'-((8-hydroxy-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methylene)-5-(thiophen-2-yl)oxazole-4-carbohydrazide (TOQ) was synthesized and found to emit yellowish green fluorescence upon introduction of In3+. Furthermore, the resulting complex TOQ-In3+ was quenched selectively by Fe3+. The detection limits of TOQ for In3+ and Fe3+ were 1.75 × 10-10 M and 8.45 × 10-9 M, respectively. The complex stoichiometry of TOQ with target ions was determined to be 1:2 via Job's plot analysis, which further was verified by ESI-MS titration and theoretical calculations. Moreover, TOQ can be used for the determination of target ions in environmental water samples. A portable paper sensor of TOQ was successfully developed for detecting In3+ to assess its applicability.
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BACKGROUND: The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS: This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS: A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7â±â14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30â±â0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS: Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
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Hipopotassemia , Falência Renal Crônica , Potássio , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População do Leste Asiático , Hipopotassemia/epidemiologia , Hipopotassemia/etiologia , Falência Renal Crônica/mortalidade , Potássio/sangue , Estudos Prospectivos , Diálise Renal , Albumina Sérica/análiseRESUMO
The C-C motif chemokine ligand 2 (CCL2) has been implicated in chronic pain, but its exact mechanism of peripheral sensitization is unknown. In this study, we aimed to clarify the mechanism of CCL2 regulation of ion channels. Our behavioral experiments revealed that ZD7288, a blocker of Ih current, can inhibit CFA and CCL2-mediated mechanical and thermal nociceptive sensitization. Furthermore, patch clamp studies demonstrated that CFA-induced peripheral sensitization primarily affects the excitability of small-diameter DRG neurons. Further studies revealed that inflammatory pain caused by CFA or incubation of DRG with CCL2 mainly affected Ih currents in small-diameter DRG neurons, which were blocked by co-incubation CCR2 antagonist INCB3344 or adenylate cyclase inhibitor SQ22536. Immunohistochemical staining showed that both intraplantar injection of CFA as well as DRG injection of CCL2 resulted in significant upregulation of CCR2+/HCN2+ expression. In conclusion, we suggest in the inflammatory pain state, CCL2 can act on small-diameter DRG neurons, leading to upregulation of HCN2 expression and consequently Ih, which in turn leads to neuronal hyperexcitability.
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Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
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Plexo Braquial , Hipotermia , Neuralgia , Humanos , Camundongos , Animais , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipotermia/complicações , Hipotermia/metabolismo , Plexo Braquial/lesões , Edema/complicações , Edema/metabolismoRESUMO
BACKGROUND: Various experimental and clinical studies have reported on coronary microcirculatory dysfunction ("no-reflow" phenomenon). Nevertheless, pathogenesis and effective treatment are yet to be fully elucidated. This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow. METHODS: From September 1st, 2018 to June 30th, 2019, intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit, Tianjin Chest Hospital, respectively in no-reflow arteries (no-reflow group) and arteries with thrombolysis in myocardial infarction-3 flow (control group). At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back. The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure. Comparison between groups was made using the Student t test, Mann-Whitney U-test or Chi-square test, as appropriate. RESULTS: Intracoronary pressure in 33 no-reflow group and 26 in control group were measured. The intracoronary forward systolic pressure gradient was -1.3 (-4.8, 0.7) and 3.8 (0.8, 8.8) mmHg in no-reflow group and control group (Zâ=â-3.989, Pâ<â0.001), respectively, while the forward diastolic pressure gradient was -1.0 (-3.2, 0) and 4.6 (0, 16.5) mmHg in respective groups (Zâ=â-3.851, Pâ<â0.001). Moreover, the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication (Zâ=â-3.668, Pâ<â0.001 in systolic pressure gradient and Zâ=â-3.530, Pâ<â0.001 in diastolic pressure gradient). CONCLUSIONS: No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries. Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov (No. NCT03600259).
Assuntos
Infarto do Miocárdio/fisiopatologia , Idoso , Angioplastia Coronária com Balão , Pressão Arterial/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/terapia , Nicorandil/uso terapêutico , Fenômeno de não Refluxo/fisiopatologia , Intervenção Coronária Percutânea/métodosRESUMO
This work describes the first demonstration of nanocrystal plane dependent nonenzymatic electro-catalytic glucose activity of [Cu3(btc)2] nanocrystals with different shapes (nanocube, truncated cube, cuboctahedron, and octahedron). From electrochemical results, the obtained [Cu3(btc)2] nanocube modified electrode shows the best nonenzymatic electro-catalytic glucose activity. Interestingly, decreasing the {100} crystal planes from cubes to octahedra, changes the nonenzymatic electro-catalytic activity from highly sensitive to general.
Assuntos
Condutometria/métodos , Cobre/química , Glucose/análise , Glucose/química , Nanocompostos/química , Nanocompostos/ultraestrutura , Técnicas Biossensoriais/métodos , Catálise , Cristalização/métodos , Teste de Materiais , Compostos Orgânicos/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Co3V2O8 thin nanoplates are firstly described as a kind of electrode material for supercapacitors. More importantly, from electrochemical measurements, the obtained Co3V2O8 nanoplate electrode shows a good specific capacitance (0.5 A g(-1), 739 F g(-1)) and cycling stability (704 F g(-1) retained after 2000 cycles). This study essentially offers a new kind of metal vanadium oxides as electrochemical active material for the development of supercapacitors.
RESUMO
Cobalt phosphite (Co(11)(HPO(3))(8)(OH)(6)) microarchitectures assembled by ultralong nanoribbons are successfully synthesized by a mild hydrothermal condition without any additives. The uniform ultralong nanoribbon has a width of 100 nm and length of 20-30 µm. More importantly, Co(11)(HPO(3))(8)(OH)(6) microarchitectures are also successfully applied as an electrochemical supercapacitor with a good specific capacitance (312 F g(-1) at 1.25 A g(-1)), good rate capability and excellent cycling property (maintaining about 89.4% at 1.25 A g(-1) after 3000 cycles).