RESUMEN
Biomimetic therapeutics offer great potential for drug delivery that avoids immune recognition. However, the coated cell membrane usually hinders the cellular uptake of nanoparticles; thus, structure-changeable formulations have attracted increasing attention. Herein, we report photolytic pyropheophorbide a (PA)-inserted red blood cell (RBC) membrane-camouflaged curcumin dimeric prodrug (CUR2-TK)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles [(CUR2-TK)-PLGA@RBC-PA] for enhanced cancer therapy. In these nanoparticles, the inner core was constructed using PLGA and loaded with our synthesized reactive oxygen species (ROS)-responsive cleavable curcumin dimeric prodrug (CUR2-TK). The nanoparticles generated ROS in response to the light irradiation attributed to the incorporated PA. The ROS further triggered the lysis of the cell membrane and exposed the nanoparticles for enhanced tumor cellular uptake, and the ROS also cleaved CUR2-TK for controlled CUR drug release. Moreover, the ROS performed photodynamic therapy (PDT). The chemotherapy and PDT produced a combined effect in the treatment of cancer cells, thus enhancing anticancer therapeutic efficacy.
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Curcumina , Nanopartículas , Neoplasias , Fotoquimioterapia , Profármacos , Línea Celular Tumoral , Curcumina/farmacología , Curcumina/uso terapéutico , Membrana Eritrocítica , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Profármacos/farmacología , Profármacos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). RESULTS: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. CONCLUSION: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.
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Análisis de Costo-Efectividad , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Cisplatino , Análisis Costo-Beneficio , Neoplasias Nasofaríngeas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Autoimmune rheumatic diseases are chronic conditions affecting multiple systems and often occurring in young women of childbearing age. The diseases and the physiological characteristics of pregnancy significantly impact maternal-fetal health and pregnancy outcomes. Currently, the integration of big data with healthcare has led to the increasing popularity of using machine learning (ML) to mine clinical data for studying pregnancy complications. In this review, we introduce the basics of ML and the recent advances and trends of ML in different prediction applications for common pregnancy complications by autoimmune rheumatic diseases. Finally, the challenges and future for enhancing the accuracy, reliability, and clinical applicability of ML in prediction have been discussed. This review will provide insights into the utilization of ML in identifying and assisting clinical decision-making for pregnancy complications, while also establishing a foundation for exploring comprehensive management strategies for pregnancy and enhancing maternal and child health.
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Enfermedades Autoinmunes , Aprendizaje Automático , Complicaciones del Embarazo , Enfermedades Reumáticas , Humanos , Embarazo , Femenino , Enfermedades Reumáticas/complicaciones , Enfermedades Autoinmunes/diagnóstico , Complicaciones del Embarazo/inmunologíaRESUMEN
Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.
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Carbapenémicos , Infecciones por Bacterias Gramnegativas , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/microbiología , Unidades de Cuidados IntensivosRESUMEN
Environmental regulation policy is the main means of pollution control and emission reduction and plays an irreplaceable role in environmental governance. However, due to the competitive behavior of economic development, the local government cannot effectively use the efficiency of environmental regulation to reduce the emission of environmental pollution. Taking 284 prefecture-level cities in China from 2005 to 2016 as samples, this paper studies the strategic interaction of environmental regulation enforcement by local governments under different circumstances and its impact on environmental pollution, so as to provide reference for national overall environmental governance planning. Through the research, it is found that the strategic interaction of environmental regulation enforcement among Chinese cities is characterized by the race-to-the-top. And the strategic interaction of environmental regulation enforcement among cities of the same economic level has the strongest impact. Besides, the impact of environmental regulation on environmental pollution has different intensity in different scenarios, showing a non-positive correlation. Most importantly, the Pollution Paradise exists in some cities under special circumstances.
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Contaminación del Aire , Política Ambiental , Pueblo Asiatico , China , Ciudades , Conservación de los Recursos Naturales , HumanosRESUMEN
BACKGROUND: The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention. METHODS: The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis. RESULTS: A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14-86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1-3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1-12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5-60). CONCLUSIONS: EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.
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In recent years, as environmental degradation has become more and more serious, the Chinese government has formulated a series of environmental policies and regulations aimed at improving environmental quality. Does environmental regulation significantly inhibit environmental pollution? Environmental regulation will not only directly affect environmental pollution but also have an indirect impact on environmental pollution. This paper uses Bayesian posterior probability, the optimal model structure selection method, based on join 112 kinds of spatial econometric model structure, and the panel data of 30 provinces in China from 2003 to 2016 to study the effects of environmental regulation on environmental pollution base on the industrial agglomeration mechanism of synergy effect. The research covers the national level and four regions, including the eastern, central, western, and northeastern regions of China. The research shows that: (1) environmental regulation at the national level and in the eastern, central and northeastern regions can significantly curb environmental pollution, but the environmental pollution in the western region shows a significant trend of enhancement. (2) Increased industrial agglomeration across China has significantly worsened environmental pollution. (3) Environmental regulation and industrial agglomeration form a significant synergy effect, which has a significant positive impact on environmental pollution in regions other than northeast China, and a significant negative impact on environmental pollution intensity in northeast China.
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Política Ambiental/economía , Contaminación Ambiental/legislación & jurisprudencia , Teorema de Bayes , China , Industrias , Modelos EconométricosRESUMEN
The study of carbon emissions is of great significance for environmental change and economic development. Gender factors is an important perspective to examine the path of carbon emissions. Based on the panel data of 30 provinces in China from 2005 to 2016, this paper selects the optimal spatial measurement model structure by using the Bayesian posterior probability model structure selection method, and studies the impact of economy on carbon emissions and the influence mechanism of gender-based "synergy effect" on carbon emissions from the National level and regional levels. The research shows that the increase of economic promotes the increase of carbon emission in this region, but it has a restraining effect on the carbon emission in the surrounding areas. Moreover, gender factors have a significant positive effect on the region at the National level and the Eastern and Northeastern regions, but not significantly in other ones, and have a significant negative impact on carbon emissions in surrounding areas. Overall, the influence intensity of economy on carbon emission increases with the increase of gender in the National level and the Eastern and Northeastern, while the influence intensity of economy of peripheral regions on carbon emission in Central Region decreases with the increase of gender factors in peripheral regions.
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Dióxido de Carbono/análisis , Carbono/análisis , Desarrollo Económico/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricos , Emisiones de Vehículos , Teorema de Bayes , China , Investigación Empírica , HumanosRESUMEN
China launched the pilot construction of the carbon emission trading scheme (ETS) in 2011. The pilots have been running for many years. Does ETS significantly restrain the increase of carbon emission intensity? Based on China's panel data for provinces and industries, this paper uses the policy assessment method to evaluate the inhibition by ETS of carbon emission intensity. The assessment scope includes six provincial pilots and pilot industries covered by ETS. The results show that ETS has significant suppression of carbon emission intensity only in Beijing and Guangdong. There is no significant impact on the carbon emission intensity of Tianjin, Shanghai, Chongqing, and Hubei. Through the carbon emission intensity inhibition analysis of the industries covered by ETS from Beijing and Chongqing, the results of the production and supply of electric power, steam and hot water, petroleum processing and coking in Beijing have a significant impact on the ETS. Only the smelting and pressing of ferrous metals in Chongqing has a significant impact on the ETS.