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Oxaliplatin and capecitabine are instrumental in the adjunctive and palliative systemic management of colorectal cancer. The concurrent administration of these chemotherapeutic agents often results in adverse effects, such as nausea, vomiting, diarrhea, leukopenia, and hand-foot syndrome. However, reports of deep vein thrombosis (DVT) caused by oxaliplatin and capecitabine are scarce. In this case study, we report a rare occurrence of lower-extremity DVT triggered by synergistic oxaliplatin and capecitabine chemotherapy in a patient diagnosed with malignant colon cancer. During the initial cycle of chemotherapy, the patient demonstrated DVT within the intermuscular veins of the right calf and abnormalities in markers of coagulation function. Enlargement of the intermuscular venous thrombosis and an increase in coagulation markers were observed subsequent to the second chemotherapy cycle. From our experience of this case, we suggest that DVT is induced by oxaliplatin and capecitabine warrants vigilant attention. Risk assessment for DVT prior to chemotherapy, coupled with early detection and intervention, is crucial for DVT prevention. Furthermore, enhancing the awareness of health care professionals and patients about the potential of chemotherapy-induced DVT is of paramount importance. Consequently, this case carries significant clinical implications.
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BACKGROUND: Volatile organic compounds (VOCs) are a broad class of chemicals, and previous studies showed that VOCs could increase the risk of central nervous system disorders. However, few studies have comprehensively explored their association with depression among general adults. OBJECTIVE: We aimed to explore the association between blood VOCs and depression risk based on a large cross-sectional study of the National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed data from 3449 American adults in the NHANES 2013-2016. Survey-weighted logistic regression model was used to explore the association of ten blood VOCs with depression. Subsequently, the relative importance of the selected VOCs was determined using the XGBoost model. The weighted quantile sum (WQS) regression model was used to explore the overall association of 10 blood VOCs with depression. Subgroup analyses were performed to identify high-risk populations. Finally, restricted cubic spline (RCS) analysis was utilized to explore the dose-response relationship between blood VOCs and the risk of depression. RESULTS: XGBoost Algorithm model identified blood 2,5-dimethylfuran was the most critical variable in depression. The logistic regression model showed that blood benzene, blood 2,5-dimethylfuran, and blood furan showed a positive correlation with depression. In subgroup analysis, we found that the effects of the above VOCs on depression existed among the female, young middle-aged, and overweight-obese population. Mixture VOCs exposure was positively associated with depression risk (OR = 2.089, 95% CI: 1.299-3.361), and 2,5-dimethylfuran had the largest weights in WQS regression. RCS displayed that blood benzene, blood 2,5-dimethylfuran, and blood furan were positively associated with depression. CONCLUSION: The results of this study indicated that VOCs exposure was associated with an increased prevalence of depression in U.S. adults. Women, young and middle-aged, and overweight-obese populations are more vulnerable to VOCs.
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Exposición a Riesgos Ambientales , Compuestos Orgánicos Volátiles , Persona de Mediana Edad , Humanos , Adulto , Femenino , Estados Unidos/epidemiología , Encuestas Nutricionales , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Compuestos Orgánicos Volátiles/efectos adversos , Estudios Transversales , Benceno , Depresión/epidemiología , Sobrepeso , Obesidad/epidemiologíaRESUMEN
Methods: Observational study on 47 adult hospitalized cancer patients including 27 males and 20 females who received proton beam radiotherapy during December 2021 and August 2022. Nutritional assessments, 24 h dietary survey, handgrip strength (HGS) test, anthropometrical measurements, and hematological parameters were conducted or collected at the beginning and the completion of treatment. Results: The rate of nutritional risk and malnutrition among the total of 47 enrolled patients was 4.3% and 12.8% at the onset of proton radiation and raised up to 6.4% and 27.7% at the end of the treatment. 42.6% of patients experienced weight loss during the proton radiotherapy, and 1 of them had weight loss over 5%, and in general, the average body weight was stable over radiotherapy. The changes in patients' 24 h dietary intakes, HGS, and anthropometrical parameters, including triceps skinfold thickness (TSF), midupper arm circumference (MUAC), and midupper arm muscle circumference (MAMC), were statistically insignificant over the treatment (all p values > 0.05). The changes in patients' hematological parameters, including total protein (TP) and serum albumin (ALB), were not statistically significant over the treatment (all p values >0.05), and the level of hemoglobin (HGB) at the end of treatment was higher than that at the onset (p < 0.05). Conclusion: The results of this study demonstrated that proton radiotherapy might have a lighter effect on the nutritional status of cancer patients.
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Neoplasias , Estado Nutricional , Masculino , Adulto , Femenino , Humanos , Protones , Índice de Masa Corporal , Fuerza de la Mano , Neoplasias/radioterapia , Pérdida de PesoRESUMEN
Background: Programmed cell death protein-1 (PD-1) or its ligand PD-L1 monoclonal antibodies, opening a new era of tumor immunotherapy, and they have significantly improved the overall survival of many patients with advanced solid tumors. However, in addition to its effectiveness, we should also pay attention to its adverse effects. The instructions of the PD-1 inhibitor camrelizumab clearly indicate that reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse reaction; it is common for many immune checkpoint inhibitors (ICIs). Here we describe a case that anlotinib improved RCCEP induced by anti-PD-1 blockade camrelizumab with some focus on further management of this symptoms. Case Description: A 57-year-old man with squamous cell carcinoma of the upper lobe of the left lung, and with mediastinal lymphocyte and liver metastasis, received the fifth cycle of chemotherapy and immunotherapy with camrelizumab (200 mg, every 3 weeks). Four days after treatment with camrelizumab, the patient's face, head, neck, and chest skin had multiple scattered bright red round papules, which were diagnosed as RCCEP. The patient was treated with oral anlotinib (8 mg, once a day). After 5 days of treatment, the symptoms of RCCEP gradually eased, and the patient was discharged. Conclusions: In conclusion, we have reported a case of RCCEP induced by anti-PD-1 blockade camrelizumab. The patient was given oral anlotinib to relieve the symptoms of RCCEP. Suggesting that anlotinib could be a potential management to reduce the adverse reactions who are treated with camrelizumab. The risk for RCCEP should always be kept in mind during camrelizumab treatment.
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BACKGROUND: Our previous study suggested that palmitate (PA) induces human glomerular mesangial cells (HMCs) fibrosis. However, the mechanism is not fully understood. Recent studies suggested that transient receptor potential canonical channel 6 (TRPC6)/nuclear factor of activated T cell 2 (NFAT2) played an important role in renal fibrosis. Moreover, cluster of differentiation 36 (CD36) regulated the synthesis of TPRC6 agonist diglyceride. In the present study, we investigated whether PA induced HMCs fibrosis via TRPC6/NFAT2 mediated by CD36. METHODS: A type 2 diabetic nephropathy (DN) model was established in Sprague Dawley rats, and HMCs were stimulated with PA. Lipid accumulation and free fatty acid (FFA) uptake were measured. The expression levels of TGF-ß1, p-Smad2/3, FN, TRPC6, NFAT2 and CD36 were evaluated. The intracellular calcium concentration ([Ca2+]i) was assessed. RESULTS: FFA were elevated in type 2 DN rats with kidney fibrosis in addition to NFAT2 and CD36 expression. In vitro, PA induced HMCs fibrosis, [Ca2+]i elevation and NFAT2 activation. SKF96365 or TRPC6-siRNA could attenuate PA-induced HMCs damage. By contrast, the TRPC6 activator showed the opposite effect. Moreover, NFAT2-siRNA also suppressed PA-induced HMCs fibrosis. CD36 knockdown inhibited the PA-induced [Ca2+]i elevation and NFAT2 expression. In addition, long-term treatment with PA decreased TRPC6 expression in HMCs. CONCLUSION: The results of this study demonstrated that PA could induce the activation of the [Ca2+]i/NFAT2 signaling pathway through TRPC6, which led to HMCs fibrosis. Although activation of TRPC6 attributed to CD36-mediated lipid deposition, long-term stimulation of PA may lead to negative feedback on the expression of TPRC6.
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Antígenos CD36/metabolismo , Glomérulos Renales/patología , Células Mesangiales/patología , Factores de Transcripción NFATC/metabolismo , Palmitatos/metabolismo , Canal Catiónico TRPC6/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Nefropatías Diabéticas/metabolismo , Fibrosis , Humanos , Glomérulos Renales/citología , Glomérulos Renales/metabolismo , Masculino , Células Mesangiales/citología , Células Mesangiales/metabolismo , Ratas Sprague-DawleyRESUMEN
BACKGROUND The purpose of this study was to analyze predictive performance of MCV in midterm ischemic events among SCAD patients undergoing elective PCI. MATERIAL AND METHODS We retrospectively included 226 consecutive patients with SCAD who received elective PCI. The patients were grouped based on MCV quartile values. The prognostic significance of MCV was assessed using univariate and multivariate Cox proportional hazard regression analyses. RESULTS According to MCV quartile points (87.5 fL, 89.7 fL, and 92.4 fL, respectively), the included patients were divided into 4 groups, with an average follow-up of 34.2 months. There were 28 (48.3%) patients with stent thrombosis in the 1st quartile, 24 (29.1%) in the 2nd quartile, 18 (31.6%) in the 3rd quartile, and 15 (27.8%) in the 4th quartile (log-rank test, P=0.027). Multivariate analysis confirmed that MCV 1st quartile (HRadj=2.047, 95% CI 1.041-4.026; P=0.038), ALT (HRadj=1.013, 95% CI 1.004-1.023; P=0.004) and number of PCI vessels (HRadj=1.198 95% CI 1.013-1.415; P=0.034) were risk factors for ischemic events. The restenosis rate in patients belonging to the MCV 1st quartile was 2 times higher than that in MCV 2nd, 3rd, and 4th quartile groups (P=0.007). CONCLUSIONS MCV value may be independently correlated with restenosis in SCAD patients undergoing PCI. Low MCV predicts high risk of in-stent restenosis.
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Índices de Eritrocitos/fisiología , Intervención Coronaria Percutánea/métodos , Medición de Riesgo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón , China , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/etiología , Stents Liberadores de Fármacos , Femenino , Oclusión de Injerto Vascular/metabolismo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Stents/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The increased inï¬ux of free fatty acids (FFAs) into the kidney is a risk factor for diabetes nephropathy (DN). In the present study we investigated the effects of astragaloside IV (AS-IV) on FFA-induced lipid accumulation, oxidative stress, and activation of TGF-ß1 signaling in human glomerular mesangial cells (HMCs). METHODS: A DN model was induced in Sprague Dawley rats by the administration of a high-fat diet and streptozocin, and HMCs were stimulated with palmitate. Lipid accumulation and FFA uptake were detected using Oil Red O and BODIPY™ FL C16 staining, respectively. The expression levels of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, p22phox, and CD36 were evaluated by western blotting or immunofluorescence/immunohistochemistry. The level of reactive oxygen species (ROS) was detected using 2',7'-dichlorofluorescein diacetate and dihydroethidium. RESULTS: Exposure to palmitate induced marked lipid accumulation in HMCs, whereas co-treatment with AS-IV significantly attenuated this phenomenon. Moreover, AS-IV suppressed palmitate-induced expression of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, and p22phox, in addition to ROS production. Notably, AS-IV reduced the palmitate-induced expression of CD36 in HMCs and DN rats. Treatment of HMCs with the CD36 inhibitor, sulfo-N-succinimidyl oleate (SSO), significantly attenuated FFA uptake, oxidative stress, and fibrosis. Nevertheless, the combined use of SSO and AS-IV did not enhance the efficacy. CONCLUSION: AS-IV inhibited palmitate-induced HMCs oxidative stress and fibrosis via the downregulation of CD36 expression, mediating FFA uptake and lipid accumulation.
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Antígenos CD36/genética , Nefropatías Diabéticas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Saponinas/farmacología , Triterpenos/farmacología , Animales , Nefropatías Diabéticas/patología , Dieta Alta en Grasa/efectos adversos , Regulación hacia Abajo/efectos de los fármacos , Ácidos Grasos no Esterificados/metabolismo , Fibrosis/patología , Humanos , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/patología , Palmitatos/toxicidad , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Renal tubular injury plays an important role in the development and progression of DN. And apoptosis of renal tubular epithelial cells (RTEC) contribute to the loss of renal function, increased levels of serum creatinine (SCr), blood urea nitrogen (BUN), urine total protein to urine creatinine and microalbuminuria and reduction of creatinine clear rate (CCr). Moreover, recent findings suggested that endoplasmic reticulum (ER) stress may lead to apoptosis of renal cells. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-apoptosis. Thus, in this study we investigated the effects and mechanisms of AS-IV on apoptosis of RTEC in high-fat diets (HFD) and low-dose streptozotocin (STZ)-induced type 2 DN rats. The results showed that AS-IV (40, 80 mg/kg) could alleviate RTEC apoptosis in DN rats. Furthermore, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney were also improved by AS-IV. And AS-IV could reduce the expression of apoptosis-related proteins cleaved caspase-3, Bax/Bcl-2 ratio. ER stress-related proteins GRP78, p-PERK, ATF4 and CHOP were also inhibited by AS-IV in kidney of DN rats. Taken together, our study suggests that the protective effects of AS-IV may be related to inhibit ER stress-induced apoptosis through down-regulating the expression of p-PERK, ATF4 and CHOP. And our study provides a new theoretical basis for the clinical treatment of patients with kidney diseases.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Saponinas/farmacología , Triterpenos/farmacología , Factor de Transcripción Activador 4/genética , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Estreptozocina , Factor de Transcripción CHOP/genética , eIF-2 Quinasa/genéticaRESUMEN
Renal tubular injury is associated with the development of diabetic nephropathy (DN) and the end-stage renal disease (ESRD). Free fatty acids (FFAs)-associated lipotoxicity contributes to injury of proximal renal tubular epithelial (HK-2) cells in diabetes. Palmitic acid (PA) which is the most abundant saturated fatty acid in FFAs is closely associated with the gradual decline of renal function. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-inflammation and anti-oxidation. In the current study, we investigated the effects of AS-IV on PA-induced apoptosis of HK-2 cells and the underlying mechanisms. The results showed that AS-IV (10, 20, 40 µmol/L) could alleviate PA-induced apoptosis of HK-2 cells. We found that AS-IV reduced the expression of Bax and cleaved-caspase3, but increased the expression of Bcl-2 and phosphorylated Nrf2 in HK-2 cells. Moreover, AS-IV reduced the level of reactive oxygen species (ROS) in the cells. Our study suggests that AS-IV could protect against PA-induced apoptosis in HK-2 cells by inhibiting ROS generation and apoptotic protein expression. This study may provide a new theoretical option for the patients with type 2 diabetes.
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Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Ácidos Grasos no Esterificados/farmacología , Túbulos Renales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Saponinas/farmacología , Triterpenos/farmacología , Caspasa 3/metabolismo , Línea Celular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Epiteliales/metabolismo , Glucosa/metabolismo , Humanos , Túbulos Renales/metabolismo , Oxidación-Reducción/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To develop a robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of 5-fluorouracil (5-FU) in blood plasma and evaluate the use of 5-FU for treatment response surveillance as well as toxicity prediction in malignant gastrointestinal tumors. METHODS: A LC-MS/MS method was used, with signal linearity, lower limits of quantitation, precision, accuracy and stability being evaluated according to guideline US Food and Drug Administration (FDA)'s guidance for industry bioanalytical method validation.Analysis of 5-FU was performed in 35 gastrointestinal cancer patients admitted to Zhongshan Hospital of Fudan University from April 2013 to December 2013. The relationship between 5-FU with toxicity and treatment effect was compared. RESULTS: The linear ranges of 5-FU was 49-9 800 ng/ml, the lower limit of quantitation was 49.0 ng/ml. The within-run and between-run coefficients of variation (CV) of 5-FU was <3% and <6%.The recovery rates of low, medium and high level quality controls were 103.36%, 88.12% and 91.26% respectively; with standard added recovery of 109.69%, 91.06% and 88.81% respectively. The control added recoveries were 112.16%, 99.12% and 92.28% respectively. The bias was -11.69%, 2.42% and -8.09% when samples were repeated freezing and thawing twice (-80 â). The results had a bias -11.97%, 1.42%, -10.91% and 0.56%, 0.14%, 3.82% when samples were kept at 2-8 â for 2 days and 14 days. In 35 gastrointestinal cancer patients, there was no correlation between initial dose of 5-FU and 44 h AUC (concentration 3.44-53.43 mg/L·h). The risk of chemotherapy-related adverse effect in 5-Fu 44 h AUC> 30 mg/L·h group was significantly higher than 44 h AUC < 30 mg/L·h group (χ(2)=12.600, P<0.01). While the chemotherapy response of AUC > 20 mg/L·h group was significantly satisfactory than AUC < 20 mg/L·h group (χ(2)=5.358, P<0.05). CONCLUSIONS: A robust and reliable LC-MS/MS method for the determination of 5-FU in blood plasma has been developed and it is suitable for clinical application. Detecting 5-FU may guide individualized treatment and predict adverse events.