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BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Fluoruracila , Inibidores de Checkpoint Imunológico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Projetos Piloto , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Reparo de Erro de Pareamento de DNA , Adulto , Instabilidade de Microssatélites , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Terapia Neoadjuvante/métodos , Microambiente Tumoral/imunologia , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do TratamentoRESUMO
Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.
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Nefropatias Diabéticas , Transição Epitelial-Mesenquimal , Proteínas de Homeodomínio , Túbulos Renais , RNA Longo não Codificante , Transição Epitelial-Mesenquimal/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Humanos , Camundongos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Glucose/metabolismo , Glucose/farmacologia , Fibrose , Camundongos Endogâmicos C57BL , Feminino , Pessoa de Meia-IdadeRESUMO
Current Environmental, Social, and Governance (ESG) rating systems encounter challenges due to their subjectivity, time lag, and inconsistent coverage, which present significant obstacles for investors in the stock market. In contrast, news reporting data, characterized by its objectivity, timeliness, publicity, and sociality, has been a crucial source of quality market information for investors. The potential of ESG-related news as a robust complement to the data sources used in existing ESG rating systems merits further exploration. This study investigates the impact of ESG-related news on the Chinese stock market, with the goal of providing compelling evidence for integrating news media into ESG assessments. By analyzing 32,296 ESG-related news articles covering 3643 companies in the Chinese market from 2015 to 2021, we utilize event study methodology to assess the market's abnormal returns in response to ESG-related news. Our findings suggest a significant market impact from ESG-related news, indicating that investors are increasingly attentive to information pertaining to ESG issues. The study also reveals that different attributes of ESG-related news have diverse effects on the market. Specifically, news with negative sentiments has the most significant impact, and investors demonstrate a stronger reaction to ESG-related news disseminated through unofficial media. Furthermore, the study highlights that enterprise heterogeneity affects the impact of ESG-related news, with companies in the secondary and tertiary industries showing higher sensitivity. Privately-owned enterprises are found to be more influenced by such news compared to state-owned enterprises. This study offers a novel perspective in evaluating corporate ESG performance using news media, proposing a more effective and objective method to assess and manage corporate sustainability in a dynamic market landscape.
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Indústrias , Projetos de Pesquisa , Comportamento SocialRESUMO
BACKGROUND: Diffusion tensor cardiac magnetic resonance (DT-CMR) imaging has great potential to characterize myocardial microarchitecture. However, its accuracy is limited by respiratory and cardiac motion and long scan times. Here, we develop and evaluate a slice-specific tracking method to improve the efficiency and accuracy of DT-CMR acquisition during free breathing. METHODS: Coronal images were obtained along with signals from a diaphragmatic navigator. Respiratory and slice displacements were obtained from the navigator signals and coronal images, respectively, and these displacements were fitted with a linear model to obtain the slice-specific tracking factors. This method was evaluated in DT-CMR examinations of 17 healthy subjects, and the results were compared with those obtained using a fixed tracking factor of 0.6. DT-CMR with breath-holding was used for reference. Quantitative and qualitative evaluation methods were used to analyze the performance of the slice-specific tracking method and the consistency between the obtained diffusion parameters. RESULTS: In the study, the slice-specific tracking factors showed an upward trend from the basal to the apical slice. Residual in-plane movements were lower in slice-specific tracking than in fixed-factor tracking (RMSE: 2.748 ± 1.171 versus 5.983 ± 2.623, P < 0.001). The diffusion parameters obtained using slice-specific tracking were not significantly different from those obtained from breath-holding acquisition (P > 0.05). CONCLUSION: In free-breathing DT-CMR imaging, the slice-specific tracking method reduced misalignment of the acquired slices. The diffusion parameters obtained using this approach were consistent with those obtained with the breath-holding technique.
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Coração , Respiração , Humanos , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Suspensão da Respiração , Imagem de Tensor de Difusão , Reprodutibilidade dos TestesRESUMO
Dissolved heavy metal pollution in the ocean is one of the most severe environmental concerns; however, the potential sources of heavy metals and the resulting health risks are not fully understood. To explore the distribution characteristics, source apportionment, and health risks of dissolved heavy metals (As, Cd, Cu, Hg, Pb, and Zn) in the Zhoushan fishing ground, this study analyzed heavy metals in surface seawater during the wet and dry seasons. The concentrations of heavy metals varied greatly between seasons, and the mean concentration in the wet season was generally higher than that in the dry season. A positive matrix factorization model coupled with correlation analysis was applied to identify promising sources of heavy metals. Four potential sources (agricultural, industrial, traffic, atmospheric deposition, and natural sources) were identified as the determinants of the accumulation of heavy metals. The health risk assessment results revealed that non-carcinogenic risk (NCR) for adults and children were acceptable (HI < 1), and carcinogenic risk (CR) were at a low level (1 × 10-6 < TCR ≤ 1 × 10-4). The source-oriented risk assessment indicated that industrial and traffic sources were the main sources of pollution, contributing 40.7 % of NCR and 27.4 % of CR, respectively. This study proposes forming reasonable, effective policies to control industrial pollution and improve the ecological environment of Zhoushan fishing grounds.
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Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Monitoramento Ambiental , Caça , Poluentes do Solo/análise , Solo , China , Metais Pesados/análise , Medição de RiscoRESUMO
Every year, influenza spreads worldwide and burdens people's health substantially. We need a reliable model to help hospitals, pharmaceutical companies, and governments better prepare for influenza outbreaks in a timely manner. However, the domain knowledge for such public health events, such as the variable influenza seasonality and occasional pandemics, poses significant challenges in predicting influenza outbreaks. The existing methods use current and historical values in a user-defined time window as input to predict future values but lack considering the situations outside the window. To address these limitations, we proposed Dynamic Virtual Graph Significance Networks (DVGSN). The graph-based algorithm can supervisedly and dynamically learn the implied knowledge from similar "infection situations" in all the historical timepoints without the limitation of time window. Furthermore, representation learning on the dynamic virtual graph can tackle the varied seasonality with pandemic-awareness without requiring domain knowledge input. The extensive experiments on real-world influenza data demonstrate that DVGSN significantly outperforms the state-of-the-art methods. To the best of our knowledge, this is the first attempt to supervisedly learn a dynamic virtual graph for time-series prediction tasks. Moreover, the proposed method has rich interpretabilities, which makes the method more acceptable in the fields of public health, life sciences, and so on. Our source code and dataset are available at https://github.com/aI-area/DVGSN.
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Influenza Humana , Humanos , Influenza Humana/epidemiologia , Pandemias , Algoritmos , Hospitais , AprendizagemRESUMO
Molecular optimization, which transforms a given input molecule X into another Y with desired properties, is essential in molecular drug discovery. The traditional approaches either suffer from sample-inefficient learning or ignore information that can be captured with the supervised learning of optimized molecule pairs. In this study, we present a novel molecular optimization paradigm, Graph Polish. In this paradigm, with the guidance of the source and target molecule pairs of the desired properties, a heuristic optimization solution can be derived: given an input molecule, we first predict which atom can be viewed as the optimization center, and then the nearby regions are optimized around this center. We then propose an effective and efficient learning framework, Teacher and Student polish, to capture the dependencies in the optimization steps. A teacher component automatically identifies and annotates the optimization centers and the preservation, removal, and addition of some parts of the molecules; a student component learns these knowledges and applies them to a new molecule. The proposed paradigm can offer an intuitive interpretation for the molecular optimization result. Experiments with multiple optimization tasks are conducted on several benchmark datasets. The proposed approach achieves a significant advantage over the six state-of-the-art baseline methods. Also, extensive studies are conducted to validate the effectiveness, explainability, and time savings of the novel optimization paradigm.
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BACKGROUND: Platelet-to-lymphocyte ratio (PLR) has been used as a potential biomarker of inflammation-related diseases, but its role in the peritoneal dialysis-related peritonitis (PDRP) is still uncertain. This study was aimed to investigate the association between PLR and the new-onset PDRP in peritoneal dialysis (PD) patients. METHODS: In this multicenter retrospective study, 1378 PD Chinese PD patients were recruited from four centers, who were divided into the high PLR group (HPG) and the low PLR group (LPG) according to the cutoff value of PLR. The correlation between PLR and the new-onset PDRP was assessed using the Cox regression model analysis. RESULTS: During follow-up, 121 new-onset PDRP events were recorded. Kaplan-Meier survival curve showed a higher risk of new-onset PDRP in the HPG (log-rank test, P < 0.001). After adjusting for confounding factors, the Cox regression model showed the risk of new-onset PDRP was higher in the HPG than that in the LPG (HR 1.689, 95%CI 1.096-2.602, P = 0.017). Competitive risk model analysis showed that significant differences still existed between the two PLR groups in the presence of other competitive events (P < 0.001). CONCLUSION: PLR is independently associated with the new-onset PDRP in PD patients.
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Diálise Peritoneal , Peritonite , Humanos , Estudos Retrospectivos , Diálise Peritoneal/efeitos adversos , Peritonite/epidemiologia , Peritonite/etiologia , Plaquetas , Linfócitos , Prognóstico , NeutrófilosRESUMO
Objective: The risk of falling increases in diabetic peripheral neuropathy (DPN) patients. As a central part, Basal ganglia play an important role in motor and balance control, but whether its involvement in DPN is unclear. Methods: Ten patients with confirmed DPN, ten diabetes patients without DPN, and ten healthy age-matched controls(HC) were recruited to undergo magnetic resonance imaging(MRI) to assess brain structure and zone adaptability. Multiscale entropy and small-world network analysis were then used to assess the complexity of the hemodynamic response signal, reflecting the adaptability of the basal ganglia. Results: There was no significant difference in brain structure among the three groups, except the duration of diabetes in DPN patients was longer (p < 0.05). The complexity of basal ganglia was significantly decreased in the DPN group compared with the non-DPN and HC group (p < 0.05), which suggested their poor adaptability. Conclusion: In the sensorimotor loop, peripheral and early central nervous lesions exist simultaneously in DPN patients. Multiscale Entropy and Small-world Network Analysis could detect basal ganglia dysfunction prior to structural changes in MRI, potentially valuable tools for early non-invasive screening and follow-up.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/diagnóstico por imagem , Neuropatias Diabéticas/etiologia , Imageamento por Ressonância Magnética , Entropia , Encéfalo/patologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologiaRESUMO
BACKGROUND: Dilation and curettage (D&C) is a basic, but important procedure with many applications in obstetrics and gynecology. Fractional D&C provides comprehensive sampling of the endocervix and subsequently the uterus. This study designs and validates a novel fractional D&C training simulator visualizing the intrauterine operation in real time and quantitatively assessing technical skills. METHOD: The fractional D&C training simulator, consisting of measurement hardware and visual software, can display the curette tip's trajectory and force in the uterus in real time. The simulator also presents assessment indices (the cervical coverage index, cervical overlap index, uterine coverage index, uterine overlap index) to indicate the completion degree and quality of surgical performance. EXPERIENCE: Seventy-five participants with three levels of D&C experience, including 26 novices, 24 intermediates, and 25 experts, were recruited to perform fractional D&C using the training simulator and asked to fill in a postprocedure questionnaire. All assessment indices of the novices were significantly lower than those of experienced surgeons (experts and intermediates) (P<.05). The simulator was highly regarded as a teaching tool and identified frequent areas of incomplete curettage even by experienced surgeons. CONCLUSION: The fractional D&C training simulator provides valuable visualized force-position feedback and quantitative evaluation and may be beneficial for surgical training.
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Dilatação e Curetagem/educação , Avaliação Educacional , Feedback Formativo , Modelos Anatômicos , Treinamento por Simulação/estatística & dados numéricos , HumanosRESUMO
AIMS: To assess possible effect of air quality improvements, we investigated the temporal change in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) associated with pollutant concentrations. METHODS: We collected daily concentrations of particulate matter (i.e., PM2.5, PM10 and PMcoarse), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and admissions for AECOPD for 21 cities in Guangdong from 2013 to 2017. We examined the association of air pollution with AECOPD admissions using two-stage time-series analysis, and estimated the annual attributable fractions, numbers, and direct hospitalization costs of AECOPD admissions with principal component analysis. RESULTS: From 2013-2017, mean daily concentrations of SO2, PM10 and PM2.5 declined by nearly 40%, 30%, and 26% respectively. As the average daily 8 h O3 concentration increased considerably, the number of days exceeding WHO target (i.e.,100 µg/m³) increased from 103 in 2015-152 in 2017. For each interquartile range increase in pollutant concentration, the relative risks of AECOPD admission at lag 0-3 were 1.093 (95% CI 1.06-1.13) for PM2.5, 1.092 (95% CI 1.08-1.11) for O3, and 1.092 (95% CI 1.05-1.14) for SO2. Attributable fractions of AECOPD admission advanced by air pollution declined from 9.5% in 2013 to 4.9% in 2016, then increased to 6.0% in 2017. A similar declining trend was observed for direct AECOPD hospitalization costs. CONCLUSION: Declined attributable hospital admissions for AECOPD may be associated with the reduction in concentrations of PM2.5, PM10 and SO2 in Guangdong, while O3 has emerged as an important risk factor. Summarizes the main finding of the workï¼ Reduction in PM may result in declined attributable hospitalizations for AECOPD, while O3 has emerged as an important risk factor following an intervention.
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Poluentes Atmosféricos/toxicidade , Poluição do Ar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Poluição do Ar/análise , Monóxido de Carbono/análise , China , Hospitais , Humanos , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Dióxido de Enxofre/análiseRESUMO
BACKGROUND AND OBJECTIVE: Frozen-thawed embryo transfer (FET) is now widely used for the treatment of infertility. For many couples and clinicians, concerns over the probability and how to increase the chance of a successful birth are very common. Currently, there is not a single model to predict the live birth outcomes for FET. To estimate the probability of live birth (PLB) in FET and to provide advice on potential treatment options by a data-driven predictive (DDP) model. METHODS: 2,189 FET cycles from Jan 2012 to Dec 2015 were recruited in a single center. 815 cycles of FET outcomes were live births and 1,374 cycles of FET outcomes failed. To verify the consistency of the DDP model, we carried out 10-fold cross-validation, and the mean and standard deviation of the accuracy were measured. Moreover, the performance of this model was evaluated by the mean and standard deviation of receiver operating characteristic curve and area under the curve (AUC). RESULTS: Nine dominant factors, including age, BMI, HOMA-IR, basal follicle stimulating hormone, basal luteinizing hormone, basal estradiol, endometrial thickness, the number of embryo transfers and the total number of embryos, were automatically extracted from 28 candidate factors. The accuracy of our prediction model is 76.9%±1.6%, and the AUC is 0.83. Then, the PLB is estimated by the random forest algorithm. On this basis, the DDP model can comprehensively traverse and dynamically visualize the impact of several factors on live birth outcomes. Finally, optimal suggestions for the treatment of patients before FET are attempted to be made by the genetic algorithm. CONCLUSION: The DDP model can not only provide satisfactory performance for predicting live birth outcomes in FET but also offer a visual estimation and simulation tool for clinicians to make treatment plans.
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Infertilidade , Nascido Vivo , Transferência Embrionária , Feminino , Humanos , Gravidez , Taxa de Gravidez , Probabilidade , Estudos RetrospectivosRESUMO
The relation of acute fluctuations of air pollution to hospital admission for bronchiectasis remained uncertain, and large-scale studies were needed. We collected daily concentrations of particulate matter (PM), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and daily hospitalizations for bronchiectasis for 21 cities across Guangdong Province from 2013 through 2017. We examined their association using two-stage time-series analysis. Our analysis was stratified by specific sub-diagnosis, sex and age group to assess potential effect modifications. Relative risks of hospitalization for bronchiectasis were 1.060 (95%CI 1.014-1.108) for PM10 at lag0-6, 1.067 (95%CI 1.020-1.116) for PM2.5 at lag0-6, 1.038 (95%CI 1.005-1.073) for PMcoarse at lag0-6, 1.058 (95%CI 1.015-1.103) for SO2 at lag0-4, 1.057 (95%CI 1.030-1.084) for NO2 at lag0 and 1.055 (95%CI 1.025-1.085) for CO at lag0-6 per interquartile range increase of air pollution. Specifically, acute fluctuations of air pollution might be a risk factor for bronchiectasis patients with lower respiratory infection but not with hemoptysis. Patients aged ≥65 years, and female patients appeared to be particularly susceptible to air pollution. Acute fluctuations of air pollution, particularly PM may increase the risk of hospital admission for bronchiectasis exacerbations, especially for the patients complicated with lower respiratory infection. This study strengthens the importance of reducing adverse impact on respiratory health of air pollution to protect vulnerable populations.
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Poluentes Atmosféricos , Poluição do Ar , Bronquiectasia , Ozônio , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Bronquiectasia/epidemiologia , China/epidemiologia , Exposição Ambiental , Feminino , Hospitalização , Hospitais , Humanos , Dióxido de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Dióxido de Enxofre/análiseRESUMO
BACKGROUND: The association between diurnal temperature range (DTR) and hospitalization for exacerbation of chronic respiratory diseases (CRD) was rarely reported. OBJECTIVES: To examine the association between DTR and daily hospital admissions for exacerbation of CRD and find out the potential effect of modifications on this association. METHOD: Data on daily hospitalization for exacerbation of chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis and meteorology measures from 2013 through 2017 were obtained from 21 cities in South China. After controlling the effects of daily mean temperature, relative humidity (RH), particulate matter < 2.5 µm diameter (PM2.5) and other confounding factors, a standard generalized additive model (GAM) with a quasi-Poisson distribution was performed to evaluate the relationships between DTR and daily hospital admissions of CRD in a two-stage strategy. Subgroup analysis was performed to find potential modifications, including seasonality and population characteristics. RESULT: Elevated risk of hospitalization for exacerbation of CRD (RR = 1.09 [95%CI: 1.08 to 1.11]) was associated with the increase in DTR (the 75th percentile versus the 25th percentile of DTR at lag0-6). The effects of DTR on hospital admissions for CRD were strong at low DTR in the hot season and high DTR in the cold season. The RR (the 75th percentile versus the 25th percentile of DTR at lag0-6) of hospitalization was 1.11 (95%CI: 1.08 to 1.12) for exacerbations of COPD and 1.09 (95%CI: 1.05 to 1.13) for asthma. The adverse effect of DTR on hospitalization for bronchiectasis was only observed in female patients (RR = 1.06 [95%CI: 1.03 to 1.10]). CONCLUSION: Our study provided additional evidence for the association between DTR and daily hospitalization for exacerbation of CRD, and these associations are especially stronger in COPD patients and in the cold season than the hot season. Preventive measures to reduce the adverse impacts of DTR were needed for CRD patients.
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Ritmo Circadiano/fisiologia , Temperatura Baixa/efeitos adversos , Hospitalização/tendências , Temperatura Alta/efeitos adversos , Transtornos Respiratórios/diagnóstico , Transtornos Respiratórios/epidemiologia , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Asma/diagnóstico , Asma/epidemiologia , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , China/epidemiologia , Doença Crônica , Cidades/epidemiologia , Cidades/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) is a rare extra-nodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis. No standardized treatment protocols have been established. Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant. However, many patients are unable to tolerate the toxicities. Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma. CASE SUMMARY: We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index. Case one was a 61-year-old man. He complained of upper abdominal pain and intermittent black stool for 2 mo. Imaging examination revealed that the intestinal wall was thickened. He received a partial excision of the small intestine. A chidamide-based combination regimen was given postoperatively. Eleven months later, he presented with recurrence in the bilateral lungs. He passed away 15 mo after his diagnosis. Case two was a 35-year-old woman who complained of abdominal distention for 1 mo. Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon. Colon perforation and septic shock occurred on the fourth day of her admission. She was treated by sigmoid colostomy. Chidamide-based combination therapy was then provided. She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis. Compared to historical data, chidamide seems to improve the prognosis of MEITL slightly. CONCLUSION: MEITL is a type of aggressive lymphoma. Chidamide is a new promising approach for the treatment of MEITL.
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Previous behavioral studies have shown that high-intensity cognitive tasks weaken balance control in elder adults. Moreover, age-related loss of plantar sensation is considered to be an important contributing factor to the occurrence of falls. Recently, we have realized that transcranial direct current stimulation (tDCS) can effectively improve the balance of the elderly under the dual-task, but its underlying regulatory mechanism is not clear. In this study, task functional Magnetic Resonance Imaging (fMRI) was used to study the brain's response to foot stimuli under foot stimuli or dual-task (foot stimuli and cognitive task) conditions to explain the effect of the addition of cognitive tasks during balance in 16 healthy elderly adults. To study whether tDCS would counteract the effect of the added cognitive task, we further compared the differences in activity of the cerebral cortices of dual-task and tDCS-dual-task conditions. The results suggested added cognitive tasks significantly attenuated the response of the brain to foot stimuli in elderly adults. Moreover, the cortex excitability weakened by cognitive tasks was significantly promoted after 20 min of tDCS. In conclusion, a portion of the resources originally used for plantar sensory processing may be assigned to the processing of the cognitive task when the cognitive tasks are added, which results in insufficient resources for plantar sensory processing. tDCS improves the ability of the brain to respond to foot stimuli by modulating the excitability of the cognitive cortex and reverses the effects of cognitive tasks.
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Encéfalo/fisiologia , Cognição , Pé/fisiologia , Equilíbrio Postural , Desempenho Psicomotor , Idoso , Excitabilidade Cortical , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Física , Córtex Somatossensorial/fisiologia , Tato , Percepção do Tato/fisiologia , Estimulação Transcraniana por Corrente ContínuaRESUMO
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.
Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Metformina/farmacologia , Ácido Oxâmico/farmacologia , Animais , Glicemia/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/fisiologia , L-Lactato Desidrogenase/antagonistas & inibidores , Ácido Láctico/sangue , Masculino , CamundongosRESUMO
Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350-750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice. Meanwhile, OXA reduced the lactate production of adipose tissue and skeletal muscle and serum lactate levels and decreased serum levels of TG, FFA, CRP, IL-6, and TNF-α in db/db mice. The PCR array showed that OXA downregulated the expression of Tnf, Il6, leptin, Cxcr3, Map2k1, and Ikbkb, and upregulated the expression of Irs2, Nfkbia, and Pde3b in the skeletal muscle of db/db mice. Interestingly, LDH-A expression increased in the islet cells of db/db mice, and both treatment of OXA and pioglitazone decreased LDH-A expression, which might be related to the improvement of insulin secretion. Taken together, increased lactate production of adipose tissue and skeletal muscle may be at least partially responsible for insulin resistance and diabetes in db/db mice. OXA improved glycemic control and insulin sensitivity in db/db mice primarily via inhibition of tissue lactate production. Oxamic acid derivatives may be a potential drug for the treatment of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Ácido Oxâmico/farmacologia , Animais , Glicemia , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Avaliação Pré-Clínica de Medicamentos , Ingestão de Alimentos , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/enzimologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , Ácido Láctico/metabolismo , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Ácido Oxâmico/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
Rapid development has led to frequent haze in Beijing. With mountains and sea surrounding Beijing, the pollution is found to be influenced by the mountain-plain breeze and sea-land breeze in complex ways. Meanwhile, the presence of aerosols may affect the surface energy balance and impact these boundary layer (BL) processes. The effects of BL processes on aerosol pollution and the feedback between aerosol and BL processes are not yet clearly understood. Thus, the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) is used to investigate the possible effects and feedbacks during a haze episode on 23 September 2011. Influenced by the onshore prevailing wind, sea-breeze, and upslope breeze, about 45% of surface particulate matter (PM)2.5 in Beijing are found to be contributed by its neighbor cities through regional transport. In the afternoon, the development of upslope breeze suppresses the growth of BL in Beijing by imposing a relatively low thermal stable layer above the BL, which exacerbates the pollution. Two kinds of feedback during the daytime are revealed as follows: (1) as the aerosols absorb and scatter the solar radiation, the surface net radiation and sensible heat flux are decreased, while BL temperature is increased, resulting in a more stable and shallower BL, which leads to a higher surface PM2.5 concentration in the morning and (2) in the afternoon, as the presence of aerosols increases the BL temperature over plains, the upslope breeze is weakened, and the boundary layer height (BLH) over Beijing is heightened, resulting in the decrease of the surface PM2.5 concentration there.