The Value of Endoscopic Exposure of Round Window in Cochlear Implant via Facial Recess

Abstract Introduction Cochlear implantation has been considered as the best treatment in patients with severe to profound hearing loss unaidable with hearing aids. The main value of endoscope-assisted cochlear implantation is improved visibility of the RW Objective to assess the value of endoscopic assisted CI surgery via facial recess approach without elevating tympanic anulus. Methods This Prospective case series study non-randomized sample was performed on 50 patients with severe to profound hearing loss unaidable with hearing aids undergoing unilateral endoscopic assisted cochlear implant surgery with round window electrode insertion Results There were 23 male and 27 female patients. Most of the cases were children (41 cases). Of those 50 patients, 39 were prelingually hearing impaired. Fourcases had various inner ear abnormalities. The standard mastoidectomy and Posterior Tympanotomy approach were used for all cases. Endoscopic identification of the RW through the PT enabled us to perform regular surgery in all cases. The current study concludes the difference between microscopic exposure and endoscopic exposure represented by Saint Tomas classification found that endoscopic exposure of round window classification is better represented by downgrading in the classification of round window exposure as type I 29(58%), type IIa 18(36%) type IIb 3 (6%) Non were type III by endoscopic exposure compared to microscopic exposure of round window is a type I 7 (14%), type II 14(28%), type IIb 22(44%) and type III 7 (14%). Conclusion Endoscopy proved a great value in exposure and identification of RW in CI surgery through posterior tympanotomy approach,

Meta-analysis of the efficacy of invisible orthodontic appliances for maxillary molar distalization in adult patients / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of invisible orthodontic appliances without brackets for the distal movement of maxillary molars to improve the ability of orthodontists to predict treatment outcomes.@*Methods@#Web of Science, Cochrane Library, Embase, PubMed, Wanfang Database, CNKI Database, and VIP Database were searched for studies investigating the efficacy of invisible orthodontic appliances for distal movement of maxillary molars in adult patients and published from database inception to August 1, 2023. A total of three researchers screened the studies and evaluated their quality and conducted a meta-analysis of those that met quality standards.@*Results@#This study included 13 pre- and postcontrol trials with a total sample size of 281 patients. The meta-analysis revealed no significant differences in the sagittal or vertical parameters of the jawbone after treatment when compared with those before treatment (P>0.05). The displacement of the first molar was MD=-2.34, 95% CI (-2.83, -1.85); the displacement was MD=-0.95, 95% CI (-1.34, -0.56); and the inclination was MD=-2.51, 95% CI (-3.56, -1.46). There was a statistically significant difference in the change in sagittal, vertical, and axial tilt of the first molar before and after treatment. After treatment, the average adduction distance of the incisors was MD=-0.82, 95% CI (-1.54, -0.09), and the decrease in lip inclination was MD=-1.61, 95% CI (-2.86, -0.36); these values were significantly different from those before treatment (P<0.05).@*Conclusion@#Invisible orthodontic appliances can effectively move the upper molars in a distal direction and control the vertical position of the molars. When the molars move further away, there is some degree of compression and distal tilt movement, which is beneficial for patients with high angles. The sagittal movement of incisors is beneficial for improving the patient's profile.

Influence of blood donors' coagulation status in apheresis platelet aggregation in vitro / 中国输血杂志

【Objective】 To investigate whether the blood donors' coagulation status may lead to apheresis platelet aggregation in vitro. 【Methods】 Thirty blood donors with aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times previously and occurred when the last time of apheresis donation were observed in aggregated group (referred to as the experimental group); Thirty donors without aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times were observed in the control group simultaneously. The basic platelet parameters in the two groups, including Plt, MPV, PDW, Pet, P-LCR were detected by automatic blood cell analyzer (BC-3000Plus), and thromboelastogram indexes including reaction time(R), kinetics time(K), kinetics of clot development(α), maximum amplitude (MA) and coagulation index(CI) were tested by Thrombosis elastography (TEG) before collection. With SPSS24.0 software, t test was used to compare the differences between the two groups. 【Results】 The CI value in experimental group was significantly different from that of the control group (0.48± 1.00 vs -0.99 ±1.96, P0.05 ) . 【Conclusion】 The coagulation status of blood donors may be an independent risk factor for the in vitro aggregation of apheresis platelets.

Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.

Mechanism of Acanthopanax senticosus injection in the treatment of ischemic stroke based on UPLC-Q-TOF-MS and network pharmacology / 国际中医中药杂志

Objective:To analyse the material basis and potential mechanism of Acanthopanax senticosus injection (ASI) in the treatment of ischemic stroke by combining UPLC-Q/TOF-MS and network pharmacology.Methods:The chemical composition of ASI was identified by UPLC-Q/TOF-MS. The Swiss Target Prediction, GeneCards and OMIM databases were used to predict the potential targets for the action of ASI in the treatment of ischemic stroke. The String database and Cytoscape software were used to construct protein interaction network maps, and the Omicshare platform was used to perform gene ontology (GO) and KEGG enrichment analysis. The DockThor platform was used for molecular docking.Results:The analysis of 53 components in ASI was firmly established and used as a basis to obtain 189 related targets of ASI for the treatment of ischemic stroke. Reverse screening showed that 25 components in ASI may be important active components in the treatment of ischemic stroke. Functional enrichment studies found that ASI may mainly regulate PI3K-Akt signaling pathway to treat ischemic stroke.Conclusion:This study preliminarily predicted the mechanism of ASI in the treatment of ischemic stroke may be related to inhibition of inflammation, antioxidant stress, promotion of angiogenesis and protection of nerve cells.

A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Predominant low Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) score in a Mexican referral center: a selection bias caused by limited-resources?

Abstract Introduction: To date, many studies have validated the Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) scoring system in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but studies from developing countries remain scarce. Objective: The aim of this study was to evaluate and categorize Mexican patients using the HCT-CI at a referral center. Methods: One hundred and nineteen consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition in Mexico City were included. Patients were classified according to the HCT-CI scores. Results: The median age was 31 years and most were males (56%). Most patients had hematological malignancies (73%) and a low HCT-CI score (72%). The non-relapse mortality and survival were predicted according to the score. Conclusions: This is one of the few studies to evaluate the HCT-CI in adults with HLA-matched donors in a developing country and our findings suggest that the high percentage of patients with a low HCT-CI scores, contrary to international reports, could be explained by different comorbidities and demographics, but mainly due to stricter filters applied to HSCT candidates and consequently, a potential selection bias caused by limited resources.

Estándares de calidad en un seguimiento a pacientes ancianos con insuficiencia cardiaca e importante comorbilidad

Resumen: Introducción: Los pacientes con insuficiencia cardiaca (IC) seguidos por los servicios de medicina interna son más ancianos y presentan más comorbilidades asociadas. Por ello presentan un riesgo elevado de ingreso hospitalario y de mortalidad. En este estudio se evaluaron los objetivos alcanzados en términos de ingresos, visitas a urgencias y mortalidad, así como la actividad realizada para conseguirlos, en una unidad dirigida a este perfil de pacientes y caracterizada por una atención integral y continuada (programa UMIPIC). Métodos: Se analizaron retrospectivamente los datos de los 329 pacientes con IC atendidos en la unidad de IC, modelo UMIPIC, del servicio de Medicina Interna del Hospital de Lugo. Se recogieron desde enero del 2020, hasta diciembre 2020 los ingresos por IC y totales, las visitas a urgencias por IC y totales, la mortalidad, las consultas realizadas, y los rescates realizados en régimen de hospital de día (HDD). Resultados: Se recogieron 108 ingresos, 40 por IC y 68 por otras causas, 99 visitas a urgencias, 25 por IC y 74 por otras causas. Se produjeron 57 fallecimientos, 37 fueron en el hospital (15 por IC, 12 por otras causas) y 20 fueron extra-hospitalarios. Se realizaron 1179 consultas médico-enfermería, 1554 consultas de enfermería exclusiva y se realizaron 406 tratamientos en HDD. Conclusiones: Los estándares de actividad y resultados conseguidos pueden ser orientativos de la actividad a desarrollar en una unidad de IC modelo UMIPIC.

Abstract: Introduction: Patients with heart failure (HF) followed by internal medicine services are older and have more associated comorbidities. For this reason, they present a high risk of hospital admission and mortality. In this study, the objectives achieved in terms of admissions, emergency room visits and mortality, as well as the activity carried out to achieve them, were evaluated in a unit aimed at this patient profile and characterized by comprehensive and continuous care (UMIPIC program). Methods: The data of the 329 patients with HF treated in the HF unit, model UMIPIC, of the Internal Medicine service of the Hospital de Lugo, were retrospectively analyzed. From January 2020, to December 2020, total and HF admissions, total and HF emergency visits, mortality, consultations made, and rescues performed in a day hospital (HDD) were collected. Results: 108 admissions were collected, 40 for HF and 68 for other causes, 99 visits to the emergency room, 25 for HF and 74 for other causes. There were 57 deaths, 37 were in the hospital (15 due to HF, 12 due to other causes) and 20 were extra-hospital. 1179 medical-nursing consultations were carried out, 1554 exclusive nursing consultations and 406 treatments were carried out in HDD. Conclusions: The activity standards and results achieved can be indicative of the activity to be carried out in an IC model UMIPIC unit.

Resumo: Introdução: Pacientes com insuficiência cardíaca (IC) acompanhados por serviços de medicina interna são mais velhos e apresentam mais comorbidades associadas. Portanto, apresentam alto risco de admissão hospitalar e mortalidade. Neste estudo, os objetivos alcançados em termos de internações, atendimentos de emergência e mortalidade, bem como a atividade desenvolvida para os atingir, foram avaliados numa unidade dirigida a este perfil de doente e caracterizada por um atendimento integral e contínuo (programa UMIPIC). Métodos: Foram analisados ​​retrospectivamente os dados dos 329 pacientes com IC atendidos na unidade de IC, modelo UMIPIC, do serviço de Clínica Médica do Hospital de Lugo. No período de janeiro de 2020 a dezembro de 2020, foram coletadas internações totais e por IC, atendimentos totais e de emergência por IC, mortalidade, consultas realizadas e resgates realizados em regime de hospital-dia (HDD). Resultados: foram coletadas 108 internações, sendo 40 por IC e 68 por outras causas, 99 visitas ao pronto-socorro, 25 por IC e 74 por outras causas. Ocorreram 57 óbitos, 37 foram hospitalares (15 por IC, 12 por outras causas) e 20 extra-hospitalares. Foram realizadas 1179 consultas médico-enfermagem, 1554 consultas exclusivas de enfermagem e 406 atendimentos em HDD. Conclusões: Os padrões de atividade e os resultados alcançados podem ser indicativos da atividade a ser desenvolvida numa unidade IC modelo UMIPIC.

Clinical Efficacy of Tiandan Tongluo Capsule Against Cerebral Infarction in Convalescence Corresponding to Stoke Due to Wind-Phlegm-Static Blood Obstructing Vessels / 中国实验方剂学杂志

Objective:To evaluate the safety and effectiveness of Tiandan Tongluo capsule in the treatment of cerebral infarction （CI） in convalescence （stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels）， with Naoshuantong capsule as a control. Method:A total of 352 convalescent patients with CI differentiated into stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels in traditional Chinese medicine （TCM） were included in this multi-center， randomized， double-blind， single-simulated， Naoshuantong capsule-controlled clinical trial， which lasted from 28 December， 2016 to 12 April， 2019. After being randomized into an experimental group and a control group at a ratio of 3∶1， patients in the experimental group were provided with oral Tiandan Tongluo capsule， five capsules per time， three times per day， whereas those in the control group received both Naoshuantong capsule simulator， two capsules per time， three times per day， and Naoshuantong capsule， three capsules per time， three times per day， for 12 successive weeks. The patients were followed up until 180 days after onset. The Barthel activities of daily living （ADL） index （BI） score was used as the primary outcome， and the secondary outcomes included neurological deficit score ［assessed with National Institutes of Health Stroke Scale （NIHSS）］， modified Rankin scale （mRS）， TCM syndrome score， and proportion of patients with new vascular events. The changes in laboratory indexes and the incidence of adverse reactions during treatment were observed. Result:Among the 389 cases enrolled， 30 dropped out， with the drop-out rate being 7.71%. There were 374 cases included in the full analysis set and 377 in the safety set. The comparison with the control group revealed that the total BI score and the percentage of BI score ≥ 75 in the experimental group were increased， but the difference was not statistically significant. The percentage of mRS score ≤ 2 within 180 days after onset in the experimental group obviously elevated in contrast to that of the control group （<italic>P</italic><0.05）. As demonstrated by TCM syndrome score analysis， the markedly effective rate in the experimental group was significantly higher than that in the control group （<italic>P</italic><0.05）. During the trial， the incidence rates of new vascular events in the experimental group and the control group were 0.00% and 1.09% （one case）， respectively， exhibiting no statistically significant difference between the two groups. Conclusion:Tiandan Tongluo capsule and Naoshuantong capsule both produce definite therapeutic effects in the treatment of CI in convalescence （stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels）. Compared with Naoshuantong capsule， Tiandan Tongluo capsule better alleviates neurological deficit， promotes neural functional recovery， and improves TCM syndrome score， without inducing severe adverse reactions.

Dosimetric investigation of non-coplanar field technology in static intensity-modulated radiation therapy for gastric carcinoma / 中国辐射卫生

Objective To compare the dosimetric characteristics of non-coplanar and coplanar field technology in static intensity-modulated radiotherapy of gastric cancer patients, so as to provide a reference for clinical radiotherapy plan selection. Methods Thirty-six patients with gastric cancer were selected to receive intensity-modulated radiotherapy in Huanggang Central Hospital, which was designed plan A and B. Group A used 7-field coplanar technology, while Group B used 7-field non-coplanar technology. We compared the differences of the optimized monitor unit, the dosimetry of organs at risk and target areas between group A and group B. Results Both group A and B could meet the requirements of doctors. The homogeneity index (0.14 ± 0.02), the conformity index (0.98 ± 0.01), Dmin (4315.21 ± 16.74) cGy、Dmean (4679.28 ± 28.39) cGy and Dmax(4952.30 ± 33.26) cGy of target areas in group B were better than those of group A. Moreover, the monitor unit of group B was much lower than that of group A, and the difference was statistically significant (P < 0.05). The Dmax, Dmean, V15, V20 and V30 of the left and right kidneys in group B were lower than those of group A. The Dmax (3408.57 ± 46.03) cGy, Dmean (1250.32 ± 14.27) cGy and V20 (44.91% ± 6.67%) of spinal cord and the Dmax (3408.57 ± 46.03) cGy, Dmean (1720.55 ± 17.42) cGy, V20 (25.31% ± 7.78%) and V30 (18.52% ± 1.56%) of small intestine were also lower than those of group A. The differences were statistically significant (P < 0.05). Conclusion The non-coplanar field radiation plan has more advantages in terms of target dose distribution and protection of organs so that it can be more considerably used in the process of planning and design.

Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca

Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity

Systemic Scleroderma with Complete Heart Block

For patients with Systemic Sclerosis (SSc), cardiac involvement (CI) is directly caused by myocardial fibrosisor ischemia or is secondary to pulmonary arterial hypertension1 Here we present a similar case of a femalepatient aged 45 yr old female who presented with complaint of recurrent syncopal attacks, and difficulty inswallowing food and liquids. She had typical CREST Syndrome manifestations with complete heart block(CHB). For which pacemaker implantation was done.

Aplicación del método bioquímico-colorimétrico para identificar agentes trypanocidas / Application of the biochemical-colorimetric method to identify trypanocidal agents

La tripanosomiasis americana es una enfermedad infecciosa desatendida, causada por el parásito protozoo Trypanosoma cruzi, que no cuenta con tratamiento en la fase crónica de esta enfermedad mortal, uno de los desafíos es encontrar terapias efectivas para esta compleja enfermedad, dado que no presenta síntomas asociables a la parasitosis por lo que es desconocida entre los médicos tradicionales. Nuestra Facultad está evaluando la medicina tradicional tacana como fuente de agentes antiparasitarios potenciales. El objetivo de este trabajo fue identificar productos naturales trypanocidas utilizando el método colorimétrico XTT-PMS. Para ello, se realizaron curvas de crecimiento de epimastigotes de T. cruzi y determinamos el tiempo óptimo de realización de los ensayos. Se seleccionó la población inicial de trabajo (3x106 parásitos/mL), las condiciones de incubación (medio LIT, 27ºC, 72 horas) y revelado (XTT-PMS, 4 horas). Con el protocolo optimizado, se realizaron evaluaciones de actividad de drogas control, controles naturales y 20 extractos crudos de plantas medicinales de la amazonía. La actividad se basó en cálculos de concentración inhibitoria media y se consideraron activos las sustancias con CI50<50µg/mL. De los 20 extractos evaluados, el 40% fueron activos. Las plantas más interesantes fueron Sipu sipu (CI50=8.9±1.7µg/mL), Ejije bid'u (CI50=9.1±1.5µg/mL) e Id'ene eidhue (CI50=10.8±1.1µg/mL) con valores de CI50 cercanos a los controles, confirmando la utilidad y potencial del protocolo desarrollado

American trypanosomiasis is listed among the unattended infectious disease, is caused by the protozoan parasite Trypanosoma cruzi, and has no treatment in the chronic phase of this deadly disease. One of the challenges is finding effective therapies for this complex disease, given that it does not present any associated symptoms to the parasitism and is unknown among traditional doctors. Our Faculty is evaluating tacana traditional medicine as a source of potential antiparasitic agents. The objective of this work was to identify trypanocidal natural products using the XTTPMS colorimetric method. For this, growth curves of T. cruzi epimastigotes were made to determine the optimal time to carry out the tests. The initial work population (3x106 parasites/mL), the incubation conditions (medium LIT, 27ºC, 72 hours) and revealed process (XTT-PMS, 4 hours) were selected. With the optimized protocol, activity evaluations of control drugs, natural controls and 20 crude extracts of medicinal plants of the Amazon were carried out. The activity was based on calculations of mean inhibitory concentration and substances with IC50 <50µg/mL were considered active. Of the 20 extracts evaluated, 40% were active. The most interesting plants were Sipu sipu (IC50=8.9±1.7µg/mL), Ejije bid'u (IC50=9.1±1.5µg/mL) and Id'ene eidhue (IC50=10.8±1.1µg/mL) with values of IC50 close to the controls, confirming the usefulness and potential of the developed protocol.

Hereditary angioedema caused by C1-esterase inhibitor deficiency: a case report with literature-based analysis

Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease caused by a mutation in the C1-inhibitor gene. It is a rare disease that is often worsened during pregnancy and childbirth. HAE, though uncommon but if untreated it may lead to maternal death.  The case report presents the successful management of a 24 years old, G2P1, with hereditary angioedema caused by C1-esterase inhibitor deficiency. This patient was managed with a multidisciplinary approach by an obstetrician, an immunologist, an anaesthesiologist and a pediatrician. She had an uneventful antenatal period, labor was induced. She had precipitate delivery and soon after delivery had a flare up of the disease. It was successfully managed with fresh frozen plasma and close observation.

Effects of ranibizumab and amfenac on the functional abilities and radiosensitivity of uveal melanoma cells / Efeitos do ranibizumabe e do amfenac nas habilidades funcionais e na radiossensibilidade de células de melanoma uveal

ABSTRACT Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

RESUMO Objetivo: Avaliar os efeitos do ranibizumabe em associação com o amfenac nas células de melanoma uveal humano e explorar a capacidade desses compostos em sensibilizar as células de melanoma uveal à radioterapia. Métodos: Células de melanoma uveal humano do tipo 92.1 foram cultivadas e submetidas ao tratamento proposto (ranibizumabe, amfenac e a combinação de ambos). Ensaios de proliferação, migração e invasão com as células de melanoma uveal do tipo 92.1 foram avaliados após tratamento com ranibizumabe (125 mg/ml), amfenac (150 nM) e a combinação de ambos. Além disso, as taxas de proliferação foram avaliadas após tratamento com ranibizumabe e amfenac com subsequente exposição das células a diferentes doses de radiação (0 Gy, 4 Gy e 8 Gy). Resultados: Ensaio de proliferação: células tratadas com ranibizumabe e amfenac combinados apresentaram taxas de proliferação inferiores em comparação ao grupo controle (p=0,016), do que as tratadas apenas com ranibizumabe (p=0,033). Ensaio de migração: foi observada uma taxa de migração significativamente mais baixa nas células tratadas com amfenac do que no grupo controle (p=0,014) e do que nas tratadas com ranibizumabe (p=0,044). Ensaio de invasão: não houve diferenças significativas entre os grupos estudados. Exposição à irradiação: no grupo da dose de 4 Gy, não houve diferença significante entre os grupos. No grupo da dose de 8 Gy, o tratamento com ranibizumabe, afenac e sua combinação antes da aplicação da radiação de 8 Gy levou a uma redução acentuada nas taxas de proliferação (p=0,009, p=0,01 e p=0,034, respectivamente) em comparação aos grupos controle. Conclusão: A combinação de ranibizumabe e amfenac reduziu a taxa de proliferação das células de melanoma uveal; no entanto, apenas o amfenac diminuiu significativamente a migração celular. A radiossensibilidade das células de melanoma uveal do tipo 92.1 aumentou após a administração de ranibizumabe, amfenac e sua combinação. Mais investigações são necessárias para determinar se esta é uma estratégia de pré-tratamento viável para tornar grandes tumores passíveis de radioterapia.

In vitro evaluation of aconitine-induced arrhythmia based on RTCA Cardio technology / 中国药理学通报

Aim To establish an in vitro arrhythmia detection technique based on real-time cell analysis (RTCA) Cardio sys-tem with aconitine as a tool drug, and to provide a reliable method for the development of antiarrhythmic drugs. Methods The effects of aconitine on rat cardiac rhythm were detected by eight-channel physiological recorder at the level of whole animal. In vitro cultured cardiac myocytes, the inoculation density of cardiac myocytes was investigated by HTCA method, the effect of aconitine on cardiac beating was monitored by RTCA Cardio system, and the CI value, beating rate, amplitude and irregular rhythm of cardiac myocytes were analyzed. Results Eight-channel physiological recorder was used to detect the effects of aconitine on whole animals. The results showed that aconitine(50 mg • g"1) could induce arrhythmias such as ventricular tachycardia, ventricular fibrillation, shortened RR interval and increased heart rate. RTCA Cardio system showed that aconitine (2-8 p,M) could induce arrhythmias such as increased cardiac cell beating frequency, decreased beating amplitude and abnormal beating state in a dose-dependent manner. Conclusions RTCA Cardio system can rapidly, sensitively and accurately detect the arrhythmia induced by aconitine in cardiac myocytes, which provides methodological reference for the development of antiarrhythmic drugs.

lncRNA HCG18 regulates the proliferation and metastasis of non-small cell lung cancer cells through targeting miR-17-5p/HMGA2 axis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanism of lncRNA HCG18/miR-17-5p/HMGA2 axis regulating the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. Methods: Sixty-two pairs of NSCLC tissues and corresponding para-cancerous tissues collected at Central Hospital of Chengde City from June 2017 to June 2018 were used for this study; in addition, NSCLC cell lines (A549, NCI-H1299, H1650, NCI-H460) and human lung epithelial BEAS-B cells were also collected. mRNA expression levels of HCG18, miR-17-5p and high-mobility group AT-hook 2 (HMGA2) in NSCLC tissues and cell lines were measured by quantitative Real-time polymerase chain reaction (qPCR). Si-HCG18, miR-17-5p, miR-17-5p+HCG18 or pcDNA3.1-HMGA2 were transfected into A549 cells and NCI-H460 cells; CCK-8 assay was used to detect the proliferation of transfected cells, Transwell assay was used to detect the migration and invasion ability of cells, and Wb was used to analyze the expressions of HMGA2 and EMT associated proteins (E-cadherin, N-cadherin and vimentin). The target relationships between HCG18 and miR-17-5p, or between miR-17-5p and HMGA2 were confirmed by dual luciferase reporter gene assay. Mice A549 cell xenograft model with HCG18 knockdown was constructed, and the growth of transplanted tumor was observed. Results: lncRNA HCG18 was highly expressed in NSCLC tissues and cells (all P<0.01); HCG18 level was significantly increased in patients at late stage or with lymphnode metastasis; and high HCG18 level was correlated with poor prognosis and low survival rates of NSCLC patients (all P<0.01). Knockdown of HCG18 significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), up-regulated E-cadherin expression but suppressed N-cadherin and vimentin expression (all P<0.01), and the volume of xenograft was obviously decreased (P<0.05). Dual luciferase reporter gene assay confirmed the relationship between HCG18 and miR-17-5p as well as miR-17-5p and HMGA2. miR-17-5p transfection significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), and up-regulated E-cadherin expression, reversely suppressed N-cadherin and vimentin expression (all P<0.01); however, miR-17-5p + HCG18 transfection reversed the effect of miR-17-5p on NSCLCcells.Conclusion:HCG18promotes the proliferationandmigrationofNSCLCcellsthrough regulating miR-17-5p/HMGA2 axis.

Inactivation of TFEB and NF-B by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.

Associação entre pico de fluxo da tosse, colonização bacteriana e estado nutricional em crianças e adolescentes com fibrose cí­stica / Association of cough peak flow with chronic bacterial colonization and nutritional status in children and adolescents with cystic fibrosis

Introdução: Este estudo teve como objetivo avaliar a associação entre pico de fluxo da tosse (PFT), colonização bacteriana crônica e estado nutricional em crianças e adolescentes com Fibrose Cí­stica. Métodos: Estudo transversal, com amostra por conveniência composta por indiví­duos com FC (7-18 anos), cadastrados em um hospital de referência estadual. Foi avaliado o PFT por um medidor portátil de pico de fluxo expiratório. Dados clí­nicos, antropométricos e sobre colonização bacteriana foram colhidos nos prontuários. O estado nutricional foi classificado pelo percentil do í­ndice de massa corporal para a idade. Para a análise estatí­stica foram usados os testes: Shapiro-Wilk, Exato de Fisher, Teste T Student independente, Mann-Whitney e Correlação de Spearman. Foi considerado significante p<0,05. Resultados: Na caracterização da amostra, houve predomí­nio das seguintes caracterí­sticas: redução do PFT (82,35%), risco nutricional (70,6%), colonização bacteriana crônica (82,4%). Indiví­duos colonizados por Pseudomonas aeruginosa apresentaram maior percentual de redução do PFT (p=0,045). Conclusão: O pico de fluxo da tosse apresentou-se reduzido nas crianças e adolescentes com FC da amostra estudada, sendo essa redução mais acentuada nos indiví­duos colonizados por Pseudomonas aeruginosa do que naqueles colonizados por Staphylococcus aureus. A maioria dos indiví­duos apresentava-se em risco nutricional, mas não foi observada correlação entre estado nutricional e pico de fluxo da tosse. (AU)

Introduction: The aim of this study was to evaluate the association among cough peak flow (CPF), chronic bacterial colonization and nutritional status in children and adolescents diagnosed with cystic fibrosis. Methods: A cross-sectional study with a convenience sample of individuals diagnosed with CF (7-18 years old) enrolled in a referral hospital of a Brazilian State. The CPF was evaluated by a portable expiratory peak flow meter. Clinical, anthropometric and bacterial colonization data were collected in the medical records. Nutritional status was classified according to the percentile of the body mass index for age. Statistical analysis was performed using the following tests: Shapiro Wilk, Fisher's Exact, Student's t, Mann-Whitney and Spearman's Correlations, being considered significant p<0.05. Results: The following characteristics predominated: CPF reduction (82.35%), nutritional risk (70.6%), chronic bacterial colonization (82.4%). Individuals colonized by Pseudomonas aeruginosa had a higher percentage of CPF reduction (p=0.045). Conclusion: The cough peak flow was reduced in the children and adolescents with cystic fibrosis in the studied sample, and this reduction was more pronounced in individuals colonized by Pseudomonas aeruginosa than in those colonized by Staphylococcus aureus. Most individuals were at nutritional risk, but no correlation was observed between nutritional status and cough peak flow. (AU)