Research on the robustness of Ethos cervical cancer online fully automatic generation of adaptive plans / 中华放射肿瘤学杂志

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

In vitro activity comparison between anti-human T lymphocyte porcine immunoglobulin prepared by Cohn ethanol fractionation and ammonium sulphate precipitation and same type of rabbit-derived products / 中国生物制品学杂志

@#Objective To compare the in vitro activity of anti-human T lymphocyte porcine immunoglobulin(P-ATG)prepared by Cohn ethanol fractionation and ammonium sulphate precipitation,commercial rabbit anti-human thymocyte immunoglobulin(trade name:Thymoglobuline),and anti-human T lymphocyte rabbit immunoglobulin(trade name:Grafalon)so as to evaluate the properties of P-ATG prepared by two processes.Methods The four products were detected for the antibody-dependent cell-mediated cytotoxicity(ADCC)by lactate dehydrogenase(LDH)method,measured for the complement dependent cytotoxicity(CDC)by CCK-8 assay,and detected for the affinity for binding with different T cell antigens(CD3,CD4,CD8)by double immunofluorescence staining method.Results Among the four products,only Thymoglobuline at the high concentration(1 mg/mL)had a weak ADCC effect on human peripheral blood mononuclear cell(PBMC).All products could induce the CDC effect in human PBMC in a dose-dependent manner,among which the effect of Thymoglobuline was higher than that of P-ATG or Grafalon preared by two processes,about 3 to 4 times,and the effect of Grafalon was comparable to that of P-ATG.In the proportion of four products binding with T cell surface antigens CD3 and CD4 was similar,However the proportion of Thymoglobuline and Grafalon binding with CD8 antigen was slightly lower than that of P-ATG.Conclusion The in vitro activity of the P-ATG prepared by Cohn ethanol fractionation and ammonium sulphate precipitation was in good agreement,and was not lower than that of imported products at the clinical dose.

Radiation dose and fractionation regimen for limited stage small cell lung cancer: a survey of current practice patterns of Chinese radiation oncologists / 中华放射肿瘤学杂志

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Thoracic radiotherapy of limited-stage small cell lung cancer : current situation of dose fractionation / 中华放射肿瘤学杂志

Thoracic radiotherapy is a major treatment and dose fractionation remains controversial in limited-stage small cell lung cancer. Twice-daily (BID) radiotherapy, as a standard protocol established in prospective studies, is often replaced by other treatment strategies in clinical practice due to the occurrence of side effects and inconvenience. In addition, in inoperable stage Ⅰ small cell lung cancer with negative lymph nodes, stereotactic ablative radiotherapy (SABR) provides a new option for some elderly patients who are expected to be unable to tolerate long-term radiotherapy. The appropriate dose fractionation scheme can both ensure the therapeutic effects and reduce toxic effects. This article reviews the research of limited-stage small cell lung cancer about dose fractionation.

Modelling the difference of circulating lymphocytes between conventional fractionation radiotherapy and stereotactic body radiation therapy for lung cancer based on convolution operation / 中华放射肿瘤学杂志

Objective:To evaluate the difference between conventional fractionation radiotherapy (CRT) and stereotactic body radiation therapy (SBRT) in lung cancer.Methods:A model was constructed based on convolution operation and finite element method, simulating the dose delivered to circulating lymphocytes (CL) in radiotherapy. The model was trained on a training group ( n=3) and validated in an independent validation group between SBRT ( n=10) and CRT ( n=10). The peak cumulative dose of circulating lymphocyte (PCDC) was compared between the two schemes, and the effect of different PTV volumes and treatment time on the cumulative dose was also analyzed. The correlation between PCDC and CL change value was discussed. Results:In the training group, PCDC with CRT to CL were 1.26 Gy,1.79 Gy, 2.54 Gy in PTV of 38 cm 3, 63 cm 3 and 114 cm 3, and PCDC with SBRT to CL were 0.84 Gy, 1.22 Gy, 1.55 Gy in PTV of 38 cm 3, 63 cm 3, 114 cm 3, respectively. PCDC gap of SBRT to CL was decreased by 0.42 Gy, 0.57 Gy, 0.99 Gy, respectively. In the validation group, the lymphocyte change value in SBRT and CRT were (1.10±0.64)×10 9/L and (0.42±0.48)×10 9/L, and there was significant difference ( P=0.015). PCDC in SBRT and CRT were 3.56 (2.79, 3.82) Gy and 1.24 (0.697, 1.73) Gy, and there was significant difference ( P<0.001). There was a positive correlation between lymphocyte change value and PCDC ( r=0.455, P<0.05). Conclusions:SBRT, compared to CRT, will lead to lower PCDC and CL lymphocyte change value, which may cause a greater impact on the difference of PCDC along with the enlargement of PTV. CRT and large PTV volume may cause more significant effect upon the body immune function.

A map of neutrophil granules by proteomics / Mapa dos neutrófilos por proteômica (OU) Mapa dos grânulos do neutrófilo por proteômica

Neutrophils are polymorphonuclear leukocytes that play a key role in the organism defense. These cells enroll in a range of actions to ensure pathogen elimination and orchestrate both innate and adaptative immune responses. The main physiological structures of neutrophils are their storage organelles that are essential since the cells activation and participate in all their functions. The storage organelles are divided into 2 types: granules and secretory vesicles. The granules are subdivided into azurophilic, specific and gelatinase. The granules are distinguished by their protein content, and since they play an important role on the neutrophil function, the knowledge of the proteins stored in these organelles can help to better understand these cells. Some proteins are present in high abundance and are used as markers for each storage organelle. These proteins are myeloperoxidase (MPO) for azurophil granules, neutrophil gelatinase associated with lipocalin-2 (NGAL) and lactoferrin (LTF) for specific granules, matrix metalloproteinase-9 (MMP9) for gelatinase granules and alkaline phosphatase (AP) for secretory vesicles. The isolation of neutrophils granules, however, is challenging and the existing procedures rely on large sample volumes, about 400 mL of peripheral blood or 3 x 108 neutrophils, not allowing for multiple biological and technical replicates. Therefore, the aim of this study was to develop a miniaturized neutrophil granules isolation method and to use biochemical assays, mass spectrometry-based proteomics and a machine learning approach to investigate the protein content of the neutrophils storage organelles. With that in mind, 40 mL of the peripheral blood of three apparently healthy volunteers were collected. The neutrophils were isolated, disrupted using nitrogen cavitation and organelles were fractionated with a discontinuous 3-layer Percoll density gradient. The presence of granules markers in each fraction was assessed using western blot , gelatin zymography and enzymatic assays. The isolation was proven successful and allowed for a reasonable separation of all neutrophils storage organelles in a gradient of less than 1 mL, about 37 times smaller than the methodsdescribed in the literature. Moreover, mass spectrometry-based proteomics identified 369 proteins in at least 3 of the 5 samples, and using a machine learning strategy, the localization of 140 proteins was predicted with confidence. Furthermore, this study was the first to investigate the proteome of neutrophil granules using technical and biological replicates, creating a reliable database for further studies. In conclusion, the developed miniaturized method is reproducible, cheaper, and reliable. In addition, it provides a resource for further studies exploring neutrophil granules protein content and mobilization during activation with different stimuli

Neutrófilos são leucócitos polimorfonucleares que possuem papel fundamental na defesa do organismo. Essas células desempenham diversas ações a fim de assegurar a eliminação de um patógeno e, além disso, orquestram a resposta imune inata e adaptativa. O conjunto composto pelos grânulos de armazenamento e as vesículas secretórias compõe a principal estrutura fisiológica dos neutrófilos. Estes componentes são essenciais desde a ativação celular, participando de todas as funcionalidades desta célula. Os grânulos são subdivididos em azurófilos, específicos e gelatinase. Eles podem ser distinguidos por meio de seu conteúdo proteico e, como são importantes na funcionalidade dos neutrófilos, identificar quais proteínas são armazenadas nestas organelas é imprescindível para entender melhor essa célula como um todo. Algumas proteínas, estão presentes de forma abundante e, portanto, são utilizadas como marcadores dos grânulos. Tais proteínas são mieloperoxidase (MPO) para os grânulos azurófilos, gelatinase de neutrófilo associada a lipocalina (NGAL) e lactoferrina (LTF) para os específicos, metaloproteinase de matrix 9 (MMP9) para os grânulos de gelatinase e fosfatase alcalina (AP) para as vesículas secretórias. Isolar estas estruturas, no entanto, é desafiador visto que os protocolos existentes na literatura utilizam grandes volumes de amostra, cerca de 400 mL de sangue ou 3 x 108 neutrófilos, para apenas um isolamento, impedindo a realização de replicatas técnicas e biológicas. Desta forma, o objetivo do presente estudo foi desenvolver um protocolo miniaturizado de isolamento dos grânulos neutrofílicos e utilizar métodos bioquímicos, de proteômica e machine learning para investigar o conteúdo proteico destas estruturas celulares. Para isto, 40 mL de sangue periférico de três voluntários aparentemente saudáveis foi coletado. Os neutrófilos foram então isolados, lisados com cavitação de nitrogênio e o fracionamento subcelular foi realizado baseado em um gradiente descontínuo de 3 camadas de Percoll. O método de isolamento foi avaliado através da investigação dos marcadores utilizando western blotting (WB), zimografia de gelatina e ensaios enzimáticos em cada fração coletada. O isolamento demonstrou-se eficiente e permitiu uma ótima separação dos grânulosem um gradiente menor que 1 mL, cerca de 37 vezes menor que os métodos atualmente descritos na literatura. Além disso, a análise proteômica foi capaz de identificar 369 proteínas presentes em pelo menos 3 das 5 réplicas investigadas e, utilizando ferramentas de machine learning, 140 proteínas foram classificadas como pertencentes a um dos tipos de grânulos ou vesícula secretória com alto nível de confiabilidade. Por fim, o presente estudo foi o primeiro a investigar o proteoma dos grânulos utilizando replicatas técnicas e biológicas, criando e fornecendo uma base de dados robusta que poderá ser utilizada em estudos futuros. Conclui-se, portanto, que a metodologia miniaturizada desenvolvida é eficaz, reprodutível e mais barata, além de permitir estudos mais complexos e profundos sobre o proteoma dos grânulos dos neutrófilos em diferentes momentos celulares, tais como quando ativados via estímulos distintos

Organic matter compartments in an Ultisol under integrated agricultural and livestock production systems in the Cerrado / Compartimentos da matéria orgânica em Argissolo sob sistemas integrados de produção agropecuária no Cerrado

Integrated agricultural production systems have the potential to increase organic matter content, which is reflected in the soil carbon (C) and nitrogen (N) concentrations. Here, we evaluated the C and N stocks and its compartments in a typical distro cohesive yellow Ultisol under the no-till (NT) and crop-livestock integration (CLI) systems, in eastern Maranhão. Five areas with different management strategies were evaluated, more specifically, one area was managed under the NT system in succession for 14 years (soybean/millet), three areas had different CLI system adoption histories (i.e., CLI was adopted 2, 4, or 8 years prior to sample collection); and finally, one area consisted of native Cerrado (savannah) vegetation. Soil samples were collected at depths of 0-0.10, 0.10-0.20, 0.20-0.30, and 0.30-0.50 m,to analyze the content and total stocks of carbon (C) and its compartments (physical and chemical), N content, soil microbial biomass, and basal respiration. Results revealed higher content and stock of C and N in areas with CLI. The principal humic substance reported was humin, and higher concentrations of C associated with minerals were present in areas under more recent CLI adoption (2 and 4 years). We demonstrated that the adoption of CLI, even if recent, leads to immediate increases in the concentrations of C and its fractions as a result of using forage crops. NT for 14 years and CLI for 8 years exhibited higher levels of C management and higher soil biological activity due to the greater stability of these systems.

Os sistemas integrados de produção agropecuária possuem potencial de incrementar a matéria orgânica, com reflexos nas concentrações de carbono e de nitrogênio no solo. O objetivo do trabalho foi avaliar estoques de carbono e nitrogênio e seus compartimentos em um Argissolo Amarelo Distrocoeso típico sob plantio direto e integração lavoura-pecuária no Leste maranhense. Os manejos avaliados foram: sistema de plantio direto em sucessão há 14 anos (soja/milheto), três áreas com diferentes históricos de sucessão com a adoção do sistema integração lavoura-pecuária (ILP), sendo dois, quatro e oito anos, além de uma área de Cerrado nativo. Foram coletadas amostras de solo nas profundidades de 0,00-0,10; 0,10-0,20; 0,20-0,30; 0,30-0,50 metros para análise de teores e estoques totais de carbono (C) e de seus compartimentos (físico e químico), nitrogênio (N) e da biomassa microbiana do solo e respiração basal. Os resultados revelam maior teor e estoque de C e N nas áreas com ILP. A substância húmica predominante foi a humina e maiores concentrações do carbono associado a minerais estiveram presentes na área sob ILP mais recente (dois e quatro anos). A adoção da ILP, mesmo que recente, proporciona incrementos imediatos nas concentrações de C e suas frações em função do emprego de forrageiras. O plantio direto há 14anos e ILP há oito anos são sistemas com maior índice de manejo do C, como, também, apresentam maior atividade biológica do solo, devido à maiores estabilidade destes sistemas.

Actividad antimicrobiana de fracciones obtenidas del aceite esencial de Minthostachys mollis frente a patógenos orales / Antimicrobial activity of fractions obtained from essential oil of Minthostachys mollis against oral pathogens

Introducción: El aceite esencial de Minthostachys mollis ha demostrado poseer importantes propiedades antimicrobianas. Objetivo: Caracterizar químicamente las fracciones obtenidas del aceite esencial de Minthostachys mollis y evaluar la actividad antimicrobiana sobre Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Porphyromonas gingivalis y Candida albicans. Material y Métodos: Las fracciones de éter de petróleo, diclorometano y metanol del AE de M. mollis fueron caracterizadas químicamente por cromatografía de gases acoplada a espectrometría de masas. Las repeticiones del ensayo antimicrobiano se calcularon con el programa EPIDAT v.4.2. La actividad antimicrobiana se realizó por el método de difusión de disco y se calculó la concentración mínima inhibitoria por el método de microdilución. Los datos fueron analizados empleando la prueba ANOVA (p=0,05). Resultados: Los principales constituyentes de las fracciones de éter de petróleo, diclorometano y metanol fueron cis-Menthone (39,8 por ciento, thymol (31,2 por ciento) y α-Terpineol (43,6 por ciento), respectivamente. Todas las cepas fueron sensibles a las tres fracciones, aunque C. albicans fue la cepa más sensible, registrando halos de inhibición de 14,73±0,57 mm para la fracción de metanol, 20,91±0,55 mm para éter de petróleo y 20,38±0,58 mm para diclorometano, se encontraron diferencias significativas cuando se compararon frente a Clorhexidina al 0,12 por ciento y Nistatina (p<0,05). Las concentraciones mínimas inhibitorias de las fracciones variaron de 0,2 a 3,2 µg/mL. Conclusiones: Los principales constituyentes de las fracciones de éter de petróleo, diclorometano y metanol fueron cis-Menthone, thymol y α-Terpineol. Las fracciones de éter de petróleo y diclorometano fueron altamente efectivas para inhibir el crecimiento de S. mutans, L. acidophilus, E. faecalis, P. gingivalis y C. albicans(AU)

Introduction: The essential oil of Minthostachys mollis has demonstrated to have important antimicrobial properties. Objective: To chemically characterize the fractions obtained from the essential oil of Minthostachys mollis and to evaluate the antimicrobial activity against Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Porphyromonas gingivalis and Candida albicans. Material and Methods: The petroleum ether, dichloromethane and methanol fractions of the AE of M. mollis were chemically characterized by gas chromatography coupled to mass spectrometry. The repetitions of the antimicrobial test were calculated using the EPIDAT v.4.2 program. The antimicrobial activity was performed by the disk diffusion method and the minimum inhibitory concentration was calculated by the microdilution method. The data were analyzed using the ANOVA test (p=0.05). Results: The main constituents of the petroleum ether, dichloromethane and methanol fractions were cis-Menthone (39,8 percent), thymol (31,2 percent)) and α-Terpineol (43,6 percent)), respectively. All strains were sensitive to the three fractions, although C. albicans was the most sensitive strain, registering inhibition halos of 14,73±0.57 mm for the methanol fraction, 20,91±0.55 mm for petroleum ether and 20.38±0.58 mm for dichloromethane, finding significant differences when compared to 0,12 percent) Chlorhexidine and Nystatin (p<0,05). The minimum inhibitory concentrations of the fractions ranged from 0,2 to 3,2 µg/mL. Conclusions: The main constituents of the petroleum ether, dichloromethane and methanol fractions were cis-Menthone, thymol and α-Terpineol. The petroleum ether and dichloromethane fractions were highly effective in inhibiting the growth of S. mutans, L. acidophilus, E. faecalis, P. gingivalis, and Calbicans(AU)

Advances in lignin valorization from a biorefinery concept / 生物工程学报

Lignin valorization for fuels and value-added products is essential to enhance the profitability and sustainability of biorefineries. Due to the complex and heterogeneous structure of lignin, technical barriers hinder the implementation of economic lignin utilization. Here, we summarize the major challenges facing lignin valorization processes. Different pretreatment methods, especially emerging combinatorial pretreatment approaches for isolating and tailoring lignin are introduced. To overcome the heterogeneity of lignin structure and improve lignin processability, advances in fractionation approaches including organosolv extraction, membrane technology, and gradient precipitation are analyzed and presented. Furthermore, progress in lignin valorization by thermochemical and biological conversion coupling with pretreatment and fractionation are systematically reviewed. Finally, we discuss advanced strategies and perspectives for future research involving biomass pretreatment, lignin fractionation and conversion processes.

Analysis of peptides and proteins from Asini Corii Colla using nano LC-Q-Exactive-MS/MS / 中国中药杂志

This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 μm×2 cm, 5 μm, C_(18)) as precolumn, Thermo Scientific EASY column(75 μm×100 mm, 3 μm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.

Comparison of altered fractionation schedule with concurrent chemo-radiation for squamous cell carcinoma of head and neck

Background: Aim of the study was to compare the response of altered fractionation schedule with concurrent chemo-radiation in patients with primary and the nodal disease.Methods: Total of 40 patients (20 in each arm) with stage 1- 4 squamous cell carcinoma of the head and neck with a performance status of 0-2 (ECOG) were included in the study. Arm A was altered fractionation schedule where in patients received 6 fractions per week to a total dose of 6600 cGy in 33 fractions. In Arm B, patients received conventional radiotherapy with concurrent chemotherapy three weekly Inj. of cisplatin (100 mg/m2). Patients were evaluated for acute toxicity every week using the Acute Radiation Morbidity Scoring Criteria. The response was assessed after 6 weeks and 12 weeks post treatment using the RECIST criteria. Data was statistically analyzed.Results: Seventeen patients in Arm A and 18 patients in Arm B completed the treatment. At the end of three months, In Arm A, 7 patients had complete response and in Arm B, 9 patients had complete response of the primary (p>0.05).  When the complete nodal response was compared in both the arms, there was no difference (2 vs 4 in Arm A vs Arm B resp.). But there were more partial nodal responders in Arm B (p = 0.016). The acute toxicities were comparable in both the arms.Conclusions: Altered fraction radiotherapy can be used in early lesions with minimal nodal burden but with locally advanced disease or large nodal burden addition of chemotherapy should not be avoided.

Extracción e identificación de lípidos polares de las microalgas Nannochloropsis oceanica y Desmodesmus asymmetricus / Extraction and identification of polar lipids from microalgae Nannochloropsis oceanica and Desmodesmus asymmetricus / Extração e identificação os lipídios polares das microalgas Nannochloropsis ocean ca e Desmodesmus asymmetricus

Resumen Los lípidos polares de las microalgas sor de gran interés debido a su aplicación como ingredientes naturales novedosos para las industrias cosmética, nutricional y farmacéutica. Por ello, el presente trabajo buscó determinar el efecto de los principales factores en la extracción e identificación de los lípidos polares de las microalgas Nannochloropsis oceanica y Desmodesmus asymmetricus, mediante el diseño de superficie de respuesta de Box-Behnken y el diseño factorial completo, respectivamente. Estas cepas del Banco de Germoplasma de Organismos Acuáticos (BGOA - IMARPE) fueron cultivadas en un invernadero, en biorreactores de 30 litros, centrifugadas y liofilizadas. Los lípidos fueron extraídos con cloroformo-metanol, fraccionados y analizados con un espectrómetro de masas Waters Xevo G2-XS QTOF. La maximización de la extracción de los lípidos totales determinó un valor óptimo de la relación masa-solvente de 25mg/3 mL, una proporción 1:1 de cloroformo-metanol, aproximadamente, y un tiempo del baño de ultrasonido entre 10 y 30 min. Los principales lípidos polares identificados para N. oceanica fueron lisofosfatidilcolina (LPC), diacilgliceril-N,N,N-trimetilhomoserina (DGTS), digalactosil diacilglicerol (DGDG) y monogalactosil diacilglicerol (MGDG) y para D. asymmetricus fueron sulfoquinovosil diacilglicerol (SQDG), LDGTS, DGTS, DGDG y MGDG.

Abstract The microalgae polar lipids are of great interest due to their application as novel natural ingredients for the cosmetic, nutritional, and pharmaceutical industry. For this reason, the present work sought to determine the effect of the main factors in the extraction and identification of polar lipids from the microalgae Nannochloropsis oceanica and Desmodesmus asymmetricus, using Box-Behnken response surface methodology design and full factorial design, respectively. These strains from the Germplasm Bank of Aquatic Organisms (BGOA - IMARPE) were grown in a greenhouse, in 30 L bioreactors, centrifuged and lyophilized. The lipids were extracted with chloroform-methanol, fractionated and analyzed with the Waters Xevo G2-XS QTOF mass spectrometer. The maximization of total lipid extraction determined an optimal value of the mass-solvent ratio of 25 mg / 3 mL, an approximate ratio of chloroform-methanol 1:1 and an ultrasound bath time between 10 and 30 min. The main polar lipids identified for the N. oceanica microalgae were lysophophatidylcholine (LPC), diacylglyceryl-N,N,N-trimethylhomoserine (DGTS), digalactosyldiacylglycerol (DGDG), and monogalactosyldiacylglycerol (MGDG) and for D. asymmetricus were sulfoquinovosyl diacylglycerol (SQDG), LDGTS, DGTS, DGDG, and MGDG.

Resumo Os lipídios polares das microalgas possuem grande interesse em sua aplicação como novos ingredientes naturais na indústria cosmética, nutricional e farmacêutica. A presente pesquisa procura determinar o efeito dos principais fatores na extração e identificação dos lipídios polares das microalgas Nannochloropsis oceanica e Desmodesmus asymmetricus, por meio do um experimento de Box-Behnken e um experimento fatorial completo, respectivamente. As cepas do Banco do Germoplasma do Organismos Aquáticos (BGOA - IMARPE), foram cultivadas em casa de vegetação, em biorreatores do 30 L, centrifugadas e liofilizadas. Os lipídios foram extraídos com clorofórmio-metanol, fracionados e analisados com o espectrómetro do massa Waters Xevo G2-XS QTOF. A maximização da extração lipídica determinou um valor ótimo da razão massa-solvente de 25 mg / 3 mL, uma proporção aproximadamente clorofórmio-metanol de 1:1 e no tempo do banho de ultrassom entre 10 e 30 minutos. Os principais lipídios polares identificados para das microalgas N. oceanica foram lisofosfatidilcolina (LPC), diacilgliceril-N,N,N-trimetil-homoserina (DGTS), digalactosil diacilglicerol (DGDG) e monogalactosil diacilglicerol (MGDG), e para D. asymmetricus foram sulfoquinovosil diacilglicerol (SQDG), LDGTS, DGTS, DGDG e MGDG.

Lattice radiation therapy - its concept and impact in the immunomodulation cancer treatment era

SUMMARY Voluminous tumors represent a challenge in radiation oncology, particularly when surgical resection is not possible. Lattice radiotherapy (LTR) is a technique that may provide equivalent or superior clinical response in the management of large tumors while limiting toxicity to adjacent normal tissues. LRT can precisely deliver inhomogeneous high doses of radiation to different areas within the gross tumor volumes (GTV). The dosimetric characteristic of LTR is defined by the ratio of the valley dose (lower doses - cold spots) and the peak doses, also called vertex (higher doses - hot spots), or the valley-to-peak dose ratio. The valley-to-peak ratio thereby quantifies the degree of spatial fractionation. LRT delivers high doses of radiation without exceeding the tolerance of adjacent critical structures. Radiobiological experiments support the role of radiation-induced bystander effects, vascular alterations, and immunologic interactions in areas subject to low dose radiation. The technological advancements continue to expand in Radiation Oncology, bringing new safety opportunities of treatment for bulky lesions.

RESUMO Tumores volumosos representam um desafio para a radio-oncologia, em especial quando a ressecção cirúrgica não é possível. A radioterapia com técnica Latisse (LTR) pode gerar resposta clínica equivalente ou superior ao tratamento convencional de grandes tumores, limitando a toxicidade nos tecidos normais adjacentes. A LRT pode fornecer com precisão altas doses não homogêneas de radiação em diferentes áreas do volume tumoral (GTV). A característica dosimétrica da LTR é definida pela razão entre a dose na região do vale (doses mais baixas - pontos frios) e as doses de pico, também chamadas de vértice (doses mais altas - pontos quentes) ou a razão da dose vale/pico. Dessa forma, a razão vale/pico quantifica o grau de fracionamento espacial da entrega de dose. A LRT entrega, dessa forma, altas doses de radiação sem exceder a tolerância de estruturas críticas adjacentes. Experimentos radiobiológicos suportam o chamado "efeito espectador" induzido por radiação, o qual promove alterações vasculares e interações imunológicas, levando à resposta tumoral mesmo em áreas expostas a baixas doses de radiação. Os avanços tecnológicos continuam a se expandir na radio-oncologia, trazendo, por meio da LTR, uma nova oportunidade segura de tratamento para lesões volumosas.

Caracterização da matéria orgânica dissolvida em processos de tratamento de água para consumo humano usando fracionamento rápido / Characterization of dissolved organic matter in drinking water treatment processes using rapid fractionation

RESUMO Matéria orgânica natural (MON) é uma complexa matriz de compostos orgânicos originados de fontes naturais que estão presentes em corpos hídricos. A MON é comprovada precursora de subprodutos da desinfecção (SPD), além de afetar processos de tratamento de água, tais como a coagulação, a desinfecção, a oxidação, a adsorção em carvão ativado e a filtração em membranas. Por essas razões, a redução da MON no tratamento de água para consumo humano é importante. Vários métodos são usados para caracterizar e quantificar a MON, tais como adsorção em resinas e parâmetros de massa. Carbono orgânico total (COT), carbono orgânico dissolvido (COD), absorção na região do ultravioleta (UV254) e absorbância específica de luz ultravioleta (AEUV) são usualmente utilizados como parâmetros de massa. O fracionamento rápido é uma técnica que usa diferentes resinas para separar frações da MON. Nesse contexto, este trabalho teve como objetivo geral caracterizar a matéria orgânica dissolvida (MOD) em processos de tratamento de água para consumo humano usando o método do fracionamento rápido e os parâmetros COD, UV254 e AEUV. Também foram analisados as variáveis turbidez, cor, pH e alcalinidade. Foram avaliados os efeitos dos processos de coagulação, sedimentação, filtração e adsorção em carvão ativado nas frações que formam a MON. Ácidos muito hidrofóbicos (AMH) constituíram a principal fração da MOD na água estudada, havendo redução de 89% entre a água bruta e o efluente do filtro de carvão ativado granular (CAG). A segunda fração predominante foi de ácidos levemente hidrofóbicos (ALH), reduzidos em 83% ao longo do tratamento. Na água bruta, as frações de matérias hidrofílicas carregadas (MHC) e de neutras (MHN) apresentaram concentrações de 0,11 mg L-1 e 0,04 mg L-1, não sendo removidas pelo tratamento.

ABSTRACT Natural organic matter (NOM) is a complex matrix of organic compounds originated from natural sources that are present in water bodies. NOM is a known precursor of disinfection by-products (DBP) and affects drinking water treatment processes such as coagulation, disinfection, oxidation, activated carbon adsorption, and membrane filtration. For these reasons, the reduction of NOM in water treatment is important. Several methods are used to characterize and quantify NOM, such as resin adsorption and mass parameters. The latter include total organic carbon (TOC), dissolved organic carbon (DOC), ultraviolet absorption at 254 nm (UV254), and specific UV absorption (SUVA). Rapid fractionation is a technique that uses different resins to separate NOM fractions. The objective of this study was to characterize dissolved organic matter (DOM) in drinking water treatment processes using rapid fractionation and the parameters DOC, UV254, and SUVA. Turbidity, color, pH, and alkalinity were also analyzed. The effects of coagulation, sedimentation, filtration, and adsorption processes on the fractions forming the NOM were evaluated. Very hydrophobic acids (VHA) constituted the main fraction of DOM in the studied water, with a reduction of 89% between raw water and granular activated carbon filter (GAC) respect to raw water. The second predominant fraction consisted of slightly hydrophobic acids (SHA), reduced by 83% throughout the treatment processes. In raw water, the hydrophilic charged (MHC) and neutral (MHN) fractions showed concentrations of 0.11 and 0.04 mg L-1, which were not removed during treatment.

A Study Comparing Different Chemoradiation Techniques in the Management of Locally Advanced Head and Neck Squamous Cell Cancers.

Concomitant chemoradiation is the treatment of choice for most of head and neck cancer patients in developing countries since these patients present in locally advanced stage. They account for 4% of all cancers. Despite treatment, loco-regional failure is seen in 51-59% patients. There is often a deferral in start of radiation therapy due to large number of cases and lesser number of existing radiation set ups. Hence, several oncologists use neo-adjuvant systemic therapy prior to external beam radiotherapy. Some oncologists prefer hypofractionated radiation therapy over conventional fractionation. Yet there is no data available comparing neoadjuvant chemotherapy followed by hypofractionation with usual concurrent chemoradiation.METHODSBiopsy proved squamous cell carcinoma of larynx and pharynx of stage III & IV excluding IVC were incorporated in this study. Patients attending Bankura Sammilani Medical College Hospital in West Bengal, were randomized to get either concurrent chemoradiation with concomitant weekly injection of cisplatin 40 mg/m2 along with an external beam radiotherapy (EBRT) dose of 70 Gy. in conventional dose fractionation; or neoadjuvant chemotherapy for three cycles with carboplatin AUC 6, injection paclitaxel 175 mg/m2 and injection 5-fluorouracil 1000 mg/m2 day 1-4 followed by hypo-fractionated EBRT (40 Gy. in 16 fractions for 3.5 weeks followed by boost dose of 20 Gy. over 8 fractions in 1.5 weeks) commenced within 3 weeks after completion of chemotherapy. Disease-free survival (DFS) at three years and complications of treatment (using version 5.0 Common-Terminology-Criteria for Adverse-Events) were compared statistically using one-way ANOVA by means of version 20 IBM SPSS Statistics® software.RESULTSCharacteristics of patients were comparable in the two arms. Acute toxicities were less after neoadjuvant chemotherapy followed by hypo fractionated radiotherapy arm. DFS and tumor control were same. Lesser treatment days made this arm more convenient to patients. This is also financially helpful in Bankura where poor patients have to stay near hospital in some rented room or they have to come regularly from long distance by hired vehicle or ambulance. Tumor control and survival advantage was same in both modalities of treatment. Thus hypo fractionated radiotherapy arm was non-inferior statistically when compared to concomitant arm in terms of tumor control and survival.CONCLUSIONSManagement by neo-adjuvant chemotherapy followed by hypo-fractionated radiation is a non-inferior apposite substitute to the usual concurrent chemo-radiation in cancer treatment centers overburdened with patients.

Enzymatic Hydrolysis Characteristics of Five Medicinal Starches by Gravitational Field-Flow Fractionation / 中国药学杂志

OBJECTIVE: To investigate the enzymatic hydrolysis characteristics of five medicinal starches, i.e.,waxy corn starch, potato starch, pea starch, wheat starch and common corn starch,using gravitational field flow fractionation (GrFFF) and other technologies. METHODS: Firstly, the enzymatic hydrolysis rates of the five medicinal starches were characterized by GrFFF, and the results of GrFFF were verified by determination of the reducing sugar.Secondly, scanning electron microscopy (SEM) and particle size analyzer were used to characterize the changes of particle morphology and size distribution during amylase hydrolysis. RESULTS: The experiments showed that the enzymatic hydrolysis rates of the five medicinal starches were successively decreased. The former two as well as the latter three reached the maximum enzymatic rate at 6-12 h and 12-24 h, respectively. As the enzymatic hydrolysis time increased, the particle size distribution range became wider and the average size increased. The results of reducing sugar quantitation, SEM and particle size analysis were almost identical to those of GrFFF. CONCLUSION: This study proves that GrFFF is an effective analytical technology to characterize the enzymatic hydrolysis of medicinal starch, which expands the application range of GrFFF and provides useful reference for the application of starch in medicine and food sciences.

Advances in chromatography-based methods for screening active compounds from natural products / 药学学报

Natural products have been a major source of leading compounds in drug discovery. How to effectively screen active compounds from complex matrix remains an interesting topic. In this review, we comprehensively summarized advanced liquid chromatography based approaches in natural products screening, including pre-column, on-column and post-column screening methods. Their advantages, disadvantages and prospect are also discussed.

Conventional Radiotherapy versus Accelerated Fractionation Radiotherapy in Squamous Cell Head and Neck Cancers – A Prospective Comparative Study

Introduction: Treatment of locally advanced lesions of head and neck cancers includes a combined modality approach suchas surgery, radiotherapy (RT), and chemotherapy.Aim: The aim of the study was to study the treatment response by locoregional control and radiation toxicity of conventionaland accelerated fractionation RT in squamous cell head and neck cancers.Materials and Methods: A total of 30 patients were included in each group, Group A received accelerated six fractions perweek and Group B received conventionally fractionated radiation therapy. The patients were assessed for locoregional diseaseresponse and radiation toxicities weekly during RT and at the end of treatment.Results: In this study, 4 patients were dropped out and 26 patients completed the treatment in each group. About 86% of thepatients in the accelerated fractionation arm and 82% of the patients in conventional arm showed complete response. Radiationtoxicities were slightly higher in accelerated fractionation compared to conventional fractionation RT.Conclusion: Accelerated fractionation with concurrent chemotherapy can be considered as an alternative treatment strategyto conventional chemoradiation.

Long-course versus short-course palliative cranial irradiation in brain metastases: a comparative study

Background: Brain metastases are the most common intracranial malignancy in adults and their management poses a significant healthcare problem. Of the various options available, whole brain radiotherapy (WBRT) remains the mainstay of treatment. Nonetheless, there is a need to develop fractionation schedules for best symptom palliation and prolonged survival. This prospective study aims to compare treatment outcome in terms of overall survival in two different WBRT schedules and determine the prognostic factors affecting this outcome.Methods: Sixty previously untreated patients with symptomatic brain metastases were randomized in two arms of 30 patients each to receive WBRT. Arm A patients received 30Gy in 10 fractions (long-course) and arm B received 20Gy in 5 fractions (short-course). All patients were assessed during and after completion of WBRT at 1, 3, 6, 9 and 12 months.Results: At 12 months post WBRT, the objective response rate i.e. complete and partial response (CR+PR) was 6.67% in arm A and 13.34% in arm B (p=0.96). Both WBRT regimens showed similar survival (p=0.65). On multivariate linear regression analysis, age ≤65 years, Karnofsky performance score (KPS) ≥70 and lack of extra-cranial metastases were significantly associated with improved survival at the end of 12 months post WBRT. EORTC QLQ-C30 showed similar improvement in quality of life in both the arms (p=0.86).Conclusions: This study suggests comparable results in the two fractionation schedules. Therefore, short-course WBRT may be used as a more convenient option in favour of shorter hospital stay and lesser burden on RT machines.

Comparison of Conventional Radiotherapy with Accelerated Fractionation Radiotherapy in Squamous Cell Head and Neck Cancers – A Prospective Study

Introduction: Head and neck carcinoma is the most commoncancer. Radiotherapy along with concurrent chemotherapyhas long been the standard nonsurgical therapy for locallyadvanced disease. State of the art regarding radiation dosefractionation has evolved from once daily treatment to hyperfractionation and accelerated fractionation. The aim of thestudy was to assess the treatment response by locoregionalcontrol and radiation toxicity resulting from conventional andaccelerated fractionation radiotherapy in squamous cell headand neck cancers.Material and methods: In both arms,25 patients wererecruited for the study .Six fractions per week of radiationwere given in Accelerated fractionation (arm A) and fivefractions in the conventional group (arm B).All patientsreceived a radiation dose of 66 Gy /200 cgy/#/in 33 fractions.No chemotherapy was administeredResults: During and immediately after the end of radiationtreatment, the patients were assessed for locoregional controland radiation toxicity .78% of the patients in acceleratedfractionation arm and 72% of the patients in conventional armshowed complete response .Radiation toxicities were slightlyhigher in accelerated fractionation compared to conventionalfractionation radiotherapyConclusion: Improved locoregional control was observed inthe accelerated arm .The radiation toxicities were higher inthe accelerated arm but they were acceptable and controllable.Overall accelerated fractionation is a better choice of radiationtreatment in squamous cell head and neck cancers.