RESUMO
AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nomogramas , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , RadiômicaRESUMO
Objective: To explore the long-term efficacy of low-dose rituximab (RTX) treatment in patients with primary membranous nephropathy (PMN). Methods: Patients with biopsy-proven PMN who received low-dose RTX as initial or second-line regimen from August 2018 to May 2020 in the Department of Nephrology, Tianjin Medical University General Hospital were respectively enrolled. The clinical parameters of patients were urinary protein>3.5 g/24 h, serum albumin<30 g/L and estimated glomerular filtration rate (eGFR)>20 ml·min-1·(1.73 m2)-1. The treatment response of patients with PMN was observed during follow-up, and the remission rate of patients with urinary protein<8 g/24 h or ≥8 g/24 h, anti-PLA2R antibody<150 RU/ml or ≥150 RU/ml, eGFR≥ 60 ml·min-1·(1.73 m2)-1 or<60 ml·min-1·(1.73 m2)-1 were analyzed, respectively. Results: A total of 40 patients were enrolled, including 26 males and 14 females, aged (53±15) years. There were 14 patients received RTX as initial treatment and 26 patients as second-line therapy. The total median dose of RTX in the first course was 800 (425, 1 075) mg. The overall remission rate at the 1st, 3rd, 6th, 12th and 24th months were 12.5% (5/40), 17.5% (7/40), 47.5% (19/40), 57.5% (23/40), 60% (24/40), respectively. The median overall response time was 6.0 (3.0, 7.5) months. Two cases relapsed. Patients with remission (n=24) had a higher level of baseline eGFR [(93.9±28.0) vs (62.4±28.1) ml·min-1·(1.73 m2)-1, P=0.001), and a lower level of both urinary protein [5.9 (5.0, 6.5) vs 11.7 (8.6, 15.5) g/24 h, P<0.001] and anti-PLA2R antibody level [73 (29, 132) vs 453 (182, 950) RU/ml, P=0.004] than those without remission (n=16) 24 month after treatment. There was no statistically significant difference in the remission rate between initial and second-line treatment (P=0.101). Moreover, patients had a higher remission rate in urinary protein<8 g/24 h group (21/26 vs 3/14, P<0.001), anti-PLA2R antibody<150 RU/ml group (16/19 vs 5/16, P=0.002) and eGFR ≥ 60 ml·min-1·(1.73 m2)-1 group (22/29 vs 2/11, P=0.003). Conclusions: Low-dose RTX treatment in PMN is effective during long-term follow-up, and has a lower recurrence rate. The results also suggest that it is more suitable for patients with baseline urinary protein<8 g/24 h, anti-PLA2R antibody<150 RU/ml and eGFR≥ 60 ml·min-1·(1.73 m2)-1.
Assuntos
Glomerulonefrite Membranosa , Feminino , Humanos , Masculino , Autoanticorpos , Taxa de Filtração Glomerular , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/metabolismo , Imunossupressores/uso terapêutico , Receptores da Fosfolipase A2 , Rituximab/uso terapêutico , Albumina Sérica/uso terapêutico , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Objective: To investigate the effects of ammonium pyrrolidine dithiocarbamate (PDTC) on tubulointerstitial inflammatory molecules and autophagy in diabetic nephropathy (DN) rats. Methods: Twenty-four male Sprague-Dawley rats were assigned to DN group (n=6) and DN+ PDTC group (n=6, PDTC, ip, 100 mg·kg-1·d-1), all received streptozotocin (STZ) 60 mg/kg intraperitoneally, and the other 12 rats were randomly divided into control group (n=6) and PDTC group (n=6). At the end of 12 weeks, after serum creatine (Scr) and 24-hour urinary protein were determined, rats were sacrificed to determined the renal pathological damages and the changes of nuclear factor (NF)-κB p65, p62, osteopontin (OPN), microtubule associated protein 1 light chain 3 (LC3)-â ¡/LC3-â , nuclear p-NF-κB p65 by immunohistological stainning and Western blot, and ultrastructural changes of autophagic process was observed by electron microscopy (EM). Results: Scr was similar among the four groups (P>0.05). The levels of urinary protein in DN group and DN + PDTC group were significantly higher than the other two groups (all P<0.01), but the level of urinary protein in DN + PDTC group was lower than that of DN group (P<0.05). DN + PDTC group had less tubulointerstitial damage compared with DN group (P<0.05). Among the four groups, expressions of p62, p65, OPN of tubulointerstitial area in DN group were significantly higher than that of the other groups (all P<0.05), and Western blot showed that DN+ PDTC group had less expressions of NF-κB p65, nuclear p-p65, OPN and more expresssion of LC3-â ¡/LC3-â compared with DN group (all P<0.05), which were consistent with the decreased autophagic vacuoles and increased mitochondria dysfunction revealed by EM. Correlation analysis showed that renal LC3-â ¡/LC3-â was negatively correlated the expressions of nuclear p-p65 and OPN (r=-0.45, P=0.02; r=-0.50, P=0.01), and p62 was positively correlated the expressions of nuclear p-p65 and OPN (r=0.33, P=0.01; r=0.41, P=0.01). Conclusion: Tubular NF-κB activation is closely related to autophagy dysfunction in DN rats, and PDTC may enhance autophagy activity in tubule cells by blocking NF-κB activity.
Assuntos
Autofagia , Nefropatias Diabéticas , Osteopontina/metabolismo , Pirrolidinas/uso terapêutico , Tiocarbamatos/uso terapêutico , Animais , Western Blotting , Rim , Masculino , NF-kappa B , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
STUDY DESIGN: Here we describe a patient who developed myelopathy due to gouty tophi of the ligamentum flavum in the thoracic spine. We also review similar cases previously reported in the literature. OBJECTIVE: Our aim was to present a case of myelopathy due to thoracic spinal gouty tophus. METHODS: We report the case of a 56-year-old male with history of peripheral gout and renal insufficiency. The patient complained of back pain and paraparesis of the left lower limb. Multiple tophi were noted over several interphalangeal and metatarsophalangeal joints. Neurological examination showed decreased left lower limb strength and a positive Babinski sign. Magnetic resonance imaging of the thoracic spine revealed hypertrophy of the ligamentum flavum at the level of T3/T4, T5/T6, T9/T10, T10/T11 and T11/T12. RESULTS: A thoracic laminectomy at T1-T5 was performed. Chalky white granular material was found in the ligamentum flavum during surgery. Histological analysis of the specimen demonstrated a gouty tophus. The patient's back pain and paraparesis of the lower left limb improved. CONCLUSION: The clinician should include spinal gout in the differential diagnosis when dealing with patients with gout and axial pain with or without neurologic deficits. If this diagnosis is seriously entertained, then a CT scan or magnetic resonance imaging as well as tissue biopsy may be needed to establish the diagnosis.
Assuntos
Ligamento Amarelo/patologia , Compressão da Medula Espinal/etiologia , Doenças da Medula Espinal/etiologia , Traumatismos da Medula Espinal/complicações , Dor nas Costas/etiologia , Gota/etiologia , Humanos , Laminectomia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compressão da Medula Espinal/cirurgia , Vértebras Torácicas/patologiaRESUMO
BACKGROUND: Immune dysfunction is very common in diabetes mellitus (DM). However, there is no evidence whether such immune dysfunction can influence the development of DM, especially the development of diabetic nephropathy (DN). AIM: To investigate the influence of absence of T cells on DN. MATERIALS AND METHODS: Balb/c nude mice and Balb/c wild-type nude (WT) mice were injected with streptozotocin (STZ). Serum tumor necrosis factor α (TNF-α), blood glucose, body weight, urine albumin/creatinine ratio and rate of kidney weight to body weight (KW/BW) were measured. RESULTS: After modeling, there was no difference of blood glucose level between nude mice and WT mice except at week 2 (28.3 ± 4.9 mmol/l vs 23.1 ± 3.9 mmol/l, p<0.01). At week 4, the serum TNF- α level of nude mice got to 175.08 ± 46.03 pg/ml (p<0.05, compared with baseline level 80.19 ± 8.46 pg/ml), whereas the TNF- α levels of WT mice was stable. At week 4, the body weight of nude mice was lower than that of WT mice (14.7 ± 3.15 g vs 17.97 ± 2.85 g, p<0.05); the urine albumin/creatinine ratio (Alb/Cr) of nude mice was higher than that of WT mice (50.96 ± 5.57 mg/mmol vs 41.09 ± 5.79 mg/mmol, p<0.05); the kidney weight to body weight of nude mice was higher than that of WT mice (0.01352 ± 0.00163 vs 0.01173 ± 0.00131, p<0.05). Correlation analysis showed urine Alb/Cr positively correlated with serum TNF-α level at week 4 (r = 0.588, p<0.01). At week 4, the increase of type IV collagen in the glomeruli was more prominent in diabetic nude mice than in diabetic WT mice (p<0.05). CONCLUSIONS: Absence of T cells in DM might influence the development of DN.
Assuntos
Diabetes Mellitus Experimental/patologia , Rim/patologia , Albuminúria/urina , Animais , Glicemia/metabolismo , Peso Corporal , Creatinina/urina , Diabetes Mellitus Experimental/imunologia , Masculino , Camundongos , Camundongos Nus , Tamanho do Órgão , Estreptozocina , Linfócitos T/fisiologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Carvedilol is a nonselective-blocking agent and is used in the treatment of hypertension and angina pectoris. OBJECTIVE: The aim of this study was to evaluate bioequivalence of two 25-mg tablet formulations of carvedilol following single oral dose in adult male volunteers. METHODS: This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 h after dosing. Plasma concentrations of Carvedilol were determined by using a validated LC-MS/MS method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-24, and AUC0-∞ was conducted to determine bioequivalence. METHODS: 23 healthy male Chinese volunteers were enrolled in the study. The mean (SD) Cmax, AUC0-24, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 73.71 (34.04) vs. 78.93 (43.64) ng/mL, 285.1 (147.0) vs. 296.9 (176.1) ng/mL · h, and 296.5 (161.4) vs. 303.4 (177.9) ng/mL · h. The 90% CIs of the ratios (test vs. reference) for the ln-transformed Cmax, AUC0-24, and AUC0 - ∞ were 85.3% to 114.3%, 90.4% to 107.6%, and 90.9% to 108.4%, respectively, meeting the criteria of SFDA, FDA and EMEA for bioequivalence. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study. CONCLUSIONS: The 90% CIs for the ratios of mean Cmax, AUC0-24, and AUC0-∞ met the regulatory criteria for bioequivalence.
Assuntos
Carbazóis/farmacocinética , Propanolaminas/farmacocinética , Carbazóis/efeitos adversos , Carbazóis/química , Carvedilol , Química Farmacêutica , Estudos Cross-Over , Humanos , Masculino , Propanolaminas/efeitos adversos , Propanolaminas/química , Comprimidos , Equivalência TerapêuticaRESUMO
Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first introduced as an antimalarial, and subsequently applied to the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers, especially in a Chinese population is limited, and this study was conducted to provide support for a generic product to obtain marketing authorization in China.The aim of the present study was to compare the pharmacokinetics and assess bioequivalence of a new generic test and the branded reference hydroxychloroquine sulfate tablets in healthy volunteers.This was a parallel, open-label, randomized, single-dose, 1-period fasting study. 54 healthy subjects were randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of the test or the reference formulation. 15 blood samples were collected and whole blood concentrations of HCQ were determined by a validated liquid chromatography-isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24 values were used to test for bioequivalence. The 2 formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%. Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events.54 healthy subjects were enrolled and completed the study (mean [SD] age, height, body weight, and BMI were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27 subjects per group. No formulation or sequence effects were observed. The mean values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6 and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The 90% CIs of the ratios of Cmax and AUC0-24 were 99.3% (98.1-102.1%), 99.7% (98.9-101.4%), respectively. 4 subjects (7.41%) experienced a total of 4 mild AEs (headache and microscopic hematuria, 1 each; and increase in plasma triglycerides, 2).The results of this study suggest that the test and reference hydroxychloroquine sulfate tablets are bioequivalent. Both formulations were generally well tolerated.
Assuntos
Antimaláricos/farmacocinética , Hidroxicloroquina/farmacocinética , Adolescente , Adulto , Antimaláricos/efeitos adversos , Área Sob a Curva , Povo Asiático , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Medicamentos Genéricos , Humanos , Hidroxicloroquina/efeitos adversos , Indicadores e Reagentes , Masculino , Espectrometria de Massas , Reprodutibilidade dos Testes , Comprimidos , Equivalência Terapêutica , Adulto JovemRESUMO
The purpose of this study was to investigate the development of the osseous acetabular index (OAI) and cartilaginous acetabular index (CAI) using MRI. The OAI and CAI were measured on the coronal MR images of the hip in 81 children with developmental dysplasia of the hip (DDH), with a mean age of 19.6 months (3 to 70), and 241 normal control children with a mean age of 5.1 years (1 month to 12.5 years). Additionally the developmental patterns of the OAI and CAI in normal children were determined by age-based cross-sectional analysis. Unlike the OAI, the normal CAI decreased rapidly from a mean of 10.17° (sd 1.60) to a mean of 8.25° (sd 1.90) within the first two years of life, and then remained constant at a mean of 8.04° (sd 1.65) until adolescence. Although no difference in OAI was found between the uninvolved hips in children with unilateral DDH and normal hips (p = 0.639), the CAI was significantly different between them both (p < 0.001). The normal CAI has fully formed at birth, and is maintained constantly throughout childhood. The CAI in the unaffected hips in children with unilateral DDH is also mildly dysplastic.
Assuntos
Acetábulo/crescimento & desenvolvimento , Cartilagem/crescimento & desenvolvimento , Luxação Congênita de Quadril/fisiopatologia , Articulação do Quadril/fisiopatologia , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Articulação do Quadril/crescimento & desenvolvimento , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
Olanzapine is a widely used agent for the treatment of schizophrenia.The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers.This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-144, and AUC0-∞ was conducted to determine bioequivalence. Adverse events were monitored, recorded and evaluated by investigators throughout the study.24 healthy male Chinese volunteers between the ages of 18-40 years with a body mass index (BMI) between 19 and 24 kg/m2 were enrolled in the study. The mean (SD) Cmax, AUC0-144, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 18.91 (5.320) vs. 18.44 (4.758) ng/mL, 582.9 (118.23) vs. 587.3 (127.12) ng/mL · h, and 615.4 (131.39) vs. 615.8 (137.45) ng/mL · h. The 90% CIs for the ratios of AUC0-144 and Cmax were 96.9% to 102.4% and 93.7% to 110.2%, respectively. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study.The 90% CIs for the ratios of mean Cmax, AUC0-144, and AUC0-∞ met the regulatory criteria for bioequivalence.
Assuntos
Antipsicóticos/farmacocinética , Benzodiazepinas/farmacocinética , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/química , Benzodiazepinas/efeitos adversos , Benzodiazepinas/química , Química Farmacêutica , Estudos Cross-Over , Humanos , Masculino , Olanzapina , Comprimidos , Equivalência Terapêutica , Adulto JovemRESUMO
The CSF and plasma concentrations of praziquantel (PZQ) were determined with high pressure liquid chromatography in 37 patients with cysticercosis of the central nervous system during a dosing regimen of PZQ 20 mg/kg p o q 8h for 3 days. The pharmacokinetic parameters were estimated using the nonlinear least squares method. The results showed that PZQ could pass through the blood-brain barrier. The absorption and elimination rates in CSF were slower than those in plasma, the corresponding mean levels being 0.1 and 0.27 micrograms/ml, which were lower than those in plasma. There was a linear correlation between CSF and plasma concentrations (r = 0.87, P less than 0.01). The neurological complications during the period of therapy were not related to the CSF level of PZQ. The cure rates of muscular and cerebral cysticerci were 14/14 and 5/37 respectively. The difference in susceptibility was considered to be caused by the pharmacokinetic behavior of PZQ and CSF and plasma. It was suggested that in general favorable regimens had better be adjusted with adequate increase of the dosage of PZQ, shortening the dosing interval, and prolong the period of PZQ treatment, but individualization of the PZQ dosing regiment would be necessary in accordance with the plasma concentration of the PZQ.