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BACKGROUD: With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients' medical costs. METHODS: A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients' perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. RESULTS: A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients' perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. CONCLUSION: By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Conduta do Tratamento Medicamentoso , Humanos , Farmacêuticos , Estudos Retrospectivos , Hospitais , Assistência Ambulatorial , Preparações FarmacêuticasRESUMO
The hypoglycemic and lipid-lowering effects of glucomannan are widely known, and it is a potential effective treatment for type II diabetes. In this study, we evaluated the effects of glucomannan supplementation on blood-lipid-related indicators, blood-glucose-related indicators, blood pressure (BP), and body weight (BW) in patients suffering from type II diabetes. We searched databases including PubMed, Cochrane, the comprehensive biomedical research database (Embase), Web of Science, and China National Knowledge Infrastructure (CNKI) for literature on glucomannan and type II diabetes. Six randomized controlled trials (RCTs) were eligible (n = 440 participants) to be included in our analysis. Glucomannan not only reduced the total cholesterol (TC) (MD -0.38 [95% CI: -0.61, -0.15], p = 0.001) and low-density lipoprotein (LDL) levels (MD -0.35 [95% CI: -0.52, -0.17], p < 0.0001) compared with the control group, but also reduced the fasting blood glucose (FBG) (MD -1.08 [95% CI: -1.65, -0.50], p = 0.0002), 2 h postprandial blood glucose (P2hBG) (MD -1.92 [95% CI: -3.19, -0.65], p = 0.003), fasting insulin (FINS) (MD -1.59 [95% CI: -2.69, -0.50], p = 0.004), and serum fructosamine (SFRA) levels (SMD -1.19 [95% CI: -1.74, -0.64], p < 0.0001). Our analysis indicates that glucomannan is an effective nutritional intervention for type II diabetes.
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Glicemia , Diabetes Mellitus Tipo 2 , Humanos , Glicemia/análise , Lipídeos , Suplementos NutricionaisRESUMO
In MOOC learning, learners' emotions have an important impact on the learning effect. In order to solve the problem that learners' emotions are not obvious in the learning process, we propose a method to identify learner emotion by combining eye movement features and scene features. This method uses an adaptive window to partition samples and enhances sample features through fine-grained feature extraction. Using an adaptive window to partition samples can make the eye movement information in the sample more abundant, and fine-grained feature extraction from an adaptive window can increase discrimination between samples. After adopting the method proposed in this paper, the four-category emotion recognition accuracy of the single modality of eye movement reached 65.1% in MOOC learning scenarios. Both the adaptive window partition method and the fine-grained feature extraction method based on eye movement signals proposed in this paper can be applied to other modalities.
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Educação a Distância , Emoções , Movimentos Oculares , AprendizagemRESUMO
Objective: The ameliorative effect of taurine on diabetes has received extensive attention in recent years. Despite promising data from animal studies, the efficacy of taurine supplementation in human studies has been inconsistent. We thus did a meta-analysis of randomized controlled trials to assess the effect of taurine supplement on glycemic indices, serum lipids, blood pressure, body composition in patients with diabetes. Methods: We systematically searched PubMed, Embase, Cochrane, Web of Science, FDA.gov, and ClinicalTrials.gov for randomized controlled trials (published from inception to January 15, 2022; no language restrictions) about the effect of taurine supplement on diabetes. Values of Standardized Mean Differences (SMD) were determined for continuous outcomes. Results: Of 2206 identified studies, 5 randomized controlled trials were eligible and were included in our analysis (N = 209 participants). Compared with the control group, taurine could significantly reduce HbA1c (SMD -0.41[95% CI: -0.74, -0.09], p = 0.01), Fasting Blood Sugar (SMD - 1.28[95% CI: -2.42, -0.14], p = 0.03) and HOMA-IR (SMD - 0.64[95% CI: -1.22, -0.06], p = 0.03). In addition, taurine also reduced Insulin (SMD -0.48 [95% CI: -0.99, 0.03], p = 0.06) and TG (SMD -0.26 [95% CI: -0.55, 0.02], p = 0.07), but did not reach statistical significance. Conclusions: Taurine supplementation is beneficial in reducing glycemic indices, such as HbA1c, Fasting Blood Sugar, HOMA-IR in diabetic patients, but has no significant effect on serum lipids, blood pressure and body composition in diabetic patients. Taurine emerges as a new option for the management of patients with diabetes. Further studies are needed to understand the potential effect of taurine in diabetic patients.
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BACKGROUND: Hypobaric hypoxia exposure leads to brain edema, followed by neuropsychological disorders. However, the related mechanism and effective treatments are still unclear. The study aimed to discuss the neuroprotective effects of Cordycepin on hypobaric hypoxia-induced cognitive impairment. METHODS: The study contained two parts. In the first part, rats underwent hypobaric hypoxia (HH) exposure for 7 days, with or without Cordycepin (10 mg/kg) or lipopolysaccharide (LPS,10 mg/kg) treatment once a day. In the second part, rats underwent HH exposure for 7 days, with or without TAK242 (3 mg/kg) and Cordycepin (10 mg/kg) once a day. Open field and Morris water maze test were performed one day after the 7days treatment. The BBB permeability was detected by the uptake of NaF. Western bloting was used to detect the levels of TLR4/MyD88/NF-κB pathway related proteins in the hippocampus. The hippocampal and serous levels of cytokines were detected by ELISA. The structure of tight junctions in the hippocampus was observed under the transmission electron microscopy. RESULTS: Both acute HH and LPS exposure could activate the TLR4 pathway and neuroinflammation, further induced BBB disruption and cognitive injury. Cordycepin could inhibit the activation of theTLR-4/NF-κB/MMP-9 pathway, which further attenuated cognitive dysfunction, and disruption of the blood-brain barrier (BBB) in HH and LPS exposed rats. Furthermore, TAK242, a TLR4 antagonist, also inhibited the activation of theTLR-4/NF-κB/MMP-9 pathway and BBB disruption, as well as attenuated HH induced cognitive impairment. CONCLUSIONS: Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway.
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Disfunção Cognitiva , NF-kappa B , Animais , Barreira Hematoencefálica/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Desoxiadenosinas , Hipóxia/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismoRESUMO
OBJECTIVE: To perform an evaluation of the risk to healthcare personnel of exposure to cisplatin during a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure in an operating room environment. METHODS: Breathing zone air samples were taken from the operating room (OR) before, during and after the procedure of HIPEC filter membrane adsorption and the liquid impact method was applied to collect air samples. The samples of surface wipe from the floor of the OR were taken after the procedure. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of cisplatin in all the samples. RESULTS: Thirty-six air samples and three surface wipes were collected from three different locations of healthcare personnel breathing zones. All the breathing zone air samples were negative for cisplatin; however, cisplatin contamination was detected on three surface wipes from the floor, but in a lowconcentration(≤ 2.25 ng). CONCLUSION: The results suggest that the risk of inhalation of cisplatin was extremely low for the healthcare personnel during the procedure of HIPEC, but the contamination of the OR floor should be taken into consideration.
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Poluentes Ocupacionais do Ar/análise , Cisplatino/análise , Quimioterapia Intraperitoneal Hipertérmica , Exposição por Inalação/análise , Exposição Ocupacional/análise , Salas Cirúrgicas/normas , Cisplatino/administração & dosagem , Monitoramento Ambiental/métodos , Pessoal de Saúde , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/métodosRESUMO
BACKGROUND: Microsurgical toe-to-hand transfer is a gold standard when it comes to repairing a thumb defect. Great toenail flap, thumbnail valva flap, free great toe, and second toe transplantation are the common methods in thumb reconstruction. Second toe transplantation achieves good function, but poor esthetics. Great toe transplantation achieves better esthetics, but hindered walking, due to the foot's loss of the great toe and moreover suboptimal thumb function. It is difficult to maintain both functional and esthetic satisfaction in thumb reconstruction. METHODS: We experimented with three different methods of toe to hand transfer. From October 2009 to July 2019, 30 patients with traumatic thumb defects received one of 3 different kinds of thumb reconstruction in our clinic according to their level of amputation. Divided evenly into three groups of ten, group one received a great toe transplantation, group two received a second toe transplantation, and group three received a combined great toenail flap and second toe phalanx transplantation. Each of the patients' thumbs had different levels of amputation at the metatarsophalangeal joint (MPJ) or distal interphalangeal joint (DIPJ). RESULTS: One patient suffered from a partial flap necrosis and received a groin flap to cover the defect. No other thumbs had any complications. The functional and esthetic results of both the donor and the recipient sites were satisfactory. Results show that, for patients with traumatic thumb defects, the combined transfer of flap and second toe phalanx was the best option. CONCLUSIONS: Compared to the great toe or second toe transfer, combined free transfer of the great toenail flap and second toe phalanx achieved a substantially better functional and esthetic result in the thumb reconstruction.
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Retalhos de Tecido Biológico/transplante , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Polegar/cirurgia , Dedos do Pé/cirurgia , Dedos do Pé/transplante , Adolescente , Adulto , Amputação Cirúrgica/métodos , Estética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polegar/lesões , Falanges dos Dedos do Pé/cirurgia , Falanges dos Dedos do Pé/transplante , Adulto JovemRESUMO
INTRODUCTION: Osteoarthritis is the most prevalent articular disease in the elderly. We aimed to explore the role of cordycepin (COR) in the progression and development of osteoarthritis and its correlation with TGF-ß activity and autophagy. METHODS: Sprague Dawley rats were induced by anterior cruciate ligament transection (ACLT) to establish knee osteoarthritis model. To investigate the role of COR in knee osteoarthritis, rats were injected with 5, 10, and 20 mg/kg of COR before joint surgery. After surgery, paw withdrawal mechanical threshold (PWMT) was performed. HE staining and Alcian blue staining were carried out to detect cartilage damage. ELISA was used to detect the level of TGFß in the serum. Protein expression was analyzed by Western blotting. RESULTS: In this study, we found that the PWMT of rats with osteoarthritis induced by ACLT was decreased significantly, accompanied by obvious histological and cartilage damage. After different doses of COR treatment, the PWMT of osteoarthritis rats induced by ACLT was increased in a dose-dependent manner. In addition, compared with the control group, COR treatment also reversed the effect of ACLT on cartilage injury in rats. Furthermore, the level of TGF-ß in serum of ACLT rats was increased significantly, which may be related to the overexpression of TGF-ß R1. However, the increase of serum TGF-ß level in ACLT rats was reversed by COR treatment in a dose-dependent manner. It is worth noting that TGF-ß overexpression reduced the proportion of autophagy-related protein LC3-II/I, thus inhibiting autophagy. In order to further confirm the effect of TGF-ß on autophagy, TGF-ß was overexpressed or the autophagy inhibitor 3-MA was applied. The results showed that TGF-ß overexpression and 3-MA treatment reversed the effect of COR on autophagy. CONCLUSION: In summary, our findings declared that COR alleviated ACLT-induced osteoarthritis pain and cartilage damage by inhibiting TGF-ß activity and inducing autophagy in rat model with knee osteoarthritis.
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Ligamento Cruzado Anterior , Desoxiadenosinas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Autofagia/efeitos dos fármacos , Desoxiadenosinas/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Injeções Intravenosas , Masculino , Medicina Tradicional Chinesa , Osteoartrite do Joelho/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
AIMS AND OBJECTIVES: To examine the influence of psycho-social and educational interventions on improving adherence to dialysis for patients with end-stage renal disease. BACKGROUND: Adherence to the complex regimen is poor, contributing to avoidable hospitalisation and morbidity. Psycho-social and educational interventions may be beneficial coping strategies. DESIGN: Systematic literature review and meta-analysis were conducted. METHODS: We conducted a systematic search of 8 databases from their inceptions to 16 January 2019 to identify relevant articles. Only randomised controlled trials (RCTs) were included in the analysis. The PRISMA checklist was used. RESULTS: A total of forty RCTs were included to evaluate the effect. The aggregated results of the studies showed that psycho-social and educational interventions elevated adherence rate in both peritoneal dialysis (PD) and haemodialysis (HD) patients. For physiological and biochemical indicators, meta-analysis revealed that significant post-treatment effects were evident for interdialytic weight gain (IDWG), IDWG/dry weight, serum potassium, phosphate, creatinine and blood urea nitrogen (BUN), except for albumin. In particular, subgroup analysis indicated that only the interventions carried out individually exerted significant combined effect for lowering IDWG. As for subjective measures, meta-analysis also revealed small but significant combined effects. CONCLUSIONS: The results of this meta-analysis suggest that psycho-social and educational interventions were associated with significant effects on adherence in patients receiving dialysis regimen. RELEVANCE TO CLINICAL PRACTICE: The analysis suggests that psycho-social and educational interventions should be considered as effective strategies for enhancing adherence to dialysis in adults with end-stage renal disease. The potential utility of these interventions should focus on how best to promote individually implementation in clinical practice.
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Cooperação do Paciente , Educação de Pacientes como Assunto/métodos , Diálise Renal/psicologia , Adulto , Feminino , Humanos , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , MasculinoRESUMO
Cancer stem cells have been identified as the major cause of cancer initiation and progression. To investigate the effects of puerarin 6â³-O-xyloside (PXY), derived from Pueraria lobata (Willd.) Ohwi, on lung cancer stem cells, we enriched and identified a subpopulation of lung cancer stem-like cells (LCSLCs) derived from lung adenocarcinoma A549 cells with traits including high self-renewal and invasive capability in vitro, elevated tumourigenicity in vivo, and high expression of stem cell markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1). We found that PXY could impair cell viability, suppress self-renewal and invasive capability, and decrease CD133, CD44 and ALDH1 mRNA expression in LCSLCs in a dose-dependent manner. Furthermore, we showed that PXY suppressed the self-renewal and invasive capability of LCSLCs at least in part through suppressing the activation of Akt/c-Myc signalling. In conclusion, PXY can block the traits of LCSLCs, indicating that PXY may be a candidate compound for lung adenocarcinoma therapy via eliminating LCSLCs.
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Autorrenovação Celular/efeitos dos fármacos , Isoflavonas/farmacologia , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células A549 , Humanos , Isoflavonas/química , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologiaRESUMO
PURPOSE: To assess the efficacy of non-pharmacological therapies for hot flushes (HFs) in women with breast cancer (BC). METHODS: Nine databases (MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), China Biology Medicine (CBM), and Wan Fang Database) were searched from their inceptions to October 2016. We also hand-searched reference lists of reviews and included articles, reviewed conference proceedings, and contacted experts. Finally, randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC. RESULTS: Sixteen trials were included in the meta-analysis. Significant combined effects of non-pharmacological therapies were observed in reducing frequency and severity of HFs after treatment (d = -0.57, P < 0.001). These effects were sustained, albeit reduced in part, during follow-up (d = -0.36, P < 0.001), with the exception of frequency (P = 0.41). Meta-analysis according to therapy types showed that for hypnosis, HFs scores instead of scores of HFs-related daily interference scale (HFRDIS) were significantly lowered at the post-treatment time point (d = -13.19, P < 0.001); for acupuncture, a small but significant effect on HFRDIS was found at the post-treatment time point (d = -3.34, P < 0.001). The effect was sustained during follow-up; however, no effect was evident for HFs frequency; for cognitive behavioral therapy (CBT), at the post-treatment time point, but not during follow-up, a small but significant effect was documented for HFs score (d = -0.88, P < 0.01). No serious adverse effect was reported in the included studies. CONCLUSIONS: Various types of non-pharmacological therapies were associated with significant effects on HFs in women with BC.
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Neoplasias da Mama/terapia , Terapias Complementares/métodos , Fogachos/terapia , Feminino , HumanosRESUMO
CONTEXT: Most cancer patients suffer from both the disease itself and symptoms induced by conventional treatment. Available literature on the clinical effects on cancer patients of acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy (TCM-FEMT) reports controversial results. OBJECTIVES: The primary objective of this meta-analysis was to evaluate the effect of acupuncture, Tuina, Tai Chi, Qigong, and TCM-FEMT on various symptoms and quality of life (QOL) in patients with cancer; risk of bias for the selected trials also was assessed. METHODS: Studies were identified by searching electronic databases (MEDLINE via both PubMed and Ovid, Cochrane Central, China National Knowledge Infrastructure, Chinese Scientific Journal Database, China Biology Medicine, and Wanfang Database). All randomized controlled trials (RCTs) using acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT published before October 2, 2014, were selected, regardless of whether the article was published in Chinese or English. RESULTS: We identified 67 RCTs (5465 patients) that met our inclusion criteria to perform this meta-analysis. Analysis results showed that a significant combined effect was observed for QOL change in patients with terminal cancer in favor of acupuncture and Tuina (Cohen's d: 0.21-4.55, P < 0.05), whereas Tai Chi and Qigong had no effect on QOL of breast cancer survivors (P > 0.05). The meta-analysis also demonstrated that acupuncture produced small-to-large effects on adverse symptoms including pain, fatigue, sleep disturbance, and some gastrointestinal discomfort; however, no significant effect was found on the frequency of hot flashes (Cohen's d = -0.02; 95% CI = -1.49 to 1.45; P = 0.97; I(2) = 36%) and mood distress (P > 0.05). Tuina relieved gastrointestinal discomfort. TCM-FEMT lowered depression level. Tai Chi improved vital capacity of breast cancer patients. High risk of bias was present in 74.63% of the selected RCTs. Major sources of risk of bias were lack of blinding, allocation concealment, and incomplete outcome data. CONCLUSION: Taken together, although there are some clear limitations regarding the body of research reviewed in this study, a tentative conclusion can be reached that acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT represent beneficial adjunctive therapies. Future study reporting in this field should be improved regarding both method and content of interventions and research methods.
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Terapia por Acupuntura , Medicina Tradicional Chinesa/métodos , Musicoterapia/métodos , Neoplasias/terapia , Qigong , Tai Chi Chuan , Gerenciamento Clínico , Humanos , Neoplasias/fisiopatologia , Neoplasias/psicologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: This study aimed to summarize the current result of controlled clinical studies published in China and analyzed the effect of psycho-oncologic interventions on distress of cancer patients. METHODS: Electronic searches were conducted in four databases. The study inclusion criteria were established on the basis of the PICOS (population, intervention, comparator, outcomes, and study design) framework. The main outcome measures were emotional distress, anxiety, and depression. Meta-analytic techniques were applied to analyze published data from the retrieved studies. RESULTS: A total of 207 controlled studies (involving 19,607 cancer patients) were included, among which 31 studies (3007 patients) were meta-analyzed. Pooled analysis showed large effects for psycho-oncologic interventions on anxiety (d = -8.71, p < 0.001) and depression (d = -8.12, p < 0.001). Health education combined with psychological support (d = -8.17, p = 0.04) or with relaxation training (d = -12.95, p < 0.001) significantly lowered the anxiety level in cancer patients. However, health education combined with relaxation training did not lower the depression levels (p > 0.05). Nurses were the primary health professionals (69.08%) responsible for delivering interventions. Meanwhile, none of the reports followed all the items of the consolidated standards of reporting trials checklist. Most studies suffered from some flaws concerning blinding, randomization procedures, participant follow-up, attrition, and so on. CONCLUSION: The findings pointed out that psycho-oncologic interventions significantly reduced distress in cancer patients of China; however, the quality of the randomized controlled trials was low. In the future, reports on controlled clinical studies should follow the consolidated standards of reporting trials statement and supply more comprehensive information.
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Sintomas Afetivos/terapia , Ansiedade/terapia , Depressão/terapia , Neoplasias/terapia , Psicoterapia/métodos , Estresse Psicológico/psicologia , Sintomas Afetivos/psicologia , Ansiedade/psicologia , China , Depressão/psicologia , Humanos , Neoplasias/psicologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Gemcitabine (GEM) is a nucleoside analog agent against a wide variety of tumors. To overcome its limitation of rapid metabolism in vivo that results in short circulation time and poor antitumor efficacy, a novel prodrug (CLA-GEM conjugate) has been developed through the covalent coupling of conjugated linoleic acid (CLA) to N(4)-amino group of GEM. The chemical structure of CLA-GEM conjugate was identified by NMR, FTIR and other methods. From in vitro tests, it was demonstrated that the linkage with CLA increased the plasma stability of GEM as well as the antitumor activity against human breast tumor cells (MCF-7). Importantly, it also altered the transport pattern of GEM across cell membrane (MCF-7 and MDA-MB-231), evidenced by the little effect of nucleoside transporter inhibitors (NBMPR and dipyridamole) on the IC(50) values of CLA-GEM, instead of the great effect on that of unmodified GEM. In vivo pharmacokinetic study showed that the CLA-GEM conjugate had a longer plasma half-life and a higher bioavailability compared to that of unmodified GEM. Significant stronger antitumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treated with CLA-GEM than that of unmodified GEM, while no significant body weight loss was found in all treatments. In conclusion, the novel CLA-GEM conjugate prepared in this study would be a promising prodrug of gemcitabine for future clinical use.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Animais , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/farmacocinética , Estabilidade de Medicamentos , Feminino , Meia-Vida , Humanos , Ácido Linoleico/farmacocinética , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Transporte de Nucleosídeos/antagonistas & inibidores , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Ratos , Ratos Sprague-Dawley , GencitabinaRESUMO
To study the incidence, the types of fusion genes and the clinical significance of rearrangements of mixed lineage leukemia (MLL) gene in acute leukemia (AL), the rearrangements of MLL gene of 60 patients with AL were detected by fluorescence in situ hybridization (FISH) and 6 types of common fusion genes resulting from the rearrangements of MLL gene were detected by nested RT-PCR. The results showed that 7 out of 60 AL patients were found the rearrangements of MLL gene, the incidence of which was 11.67%. 2 out of 7 patients were diagnosed as AML-M(5), 5 patients were diagnosed as B-ALL. The fusion genes of the 2 AML-M(5) patients who had the rearrangements of MLL gene were MLL/AF(9). Among 5 B-ALL patients, 2 patients were confirmed to express MLL/ENL, 1 patient was confirmed to express MLL/AF(4), the other 2 patients did not express the fusion genes. It is concluded that FISH is a fast, specific and sensitive method to detect the rearrangements of MLL gene in AL patients and nested RT-PCR is a convenient and feasible method to detect the types of fusion genes resulting from the rearrangements of MLL gene. The detection of MLL gene rearrangement is of great importance in predicting prognosis and guiding therapy in AL.