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INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.
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BACKGROUND: Turbo spin-echo (TSE) diffusion-weighted imaging (DWI) sequences may reduce susceptibility artifacts and image distortion in sellar region, allowing better visualization of small pituitary lesions, and may be used to assist in the diagnosis of pituitary microadenomas. PURPOSE: To explore the application value of conventional MRI combined with DWI sequences in the diagnosis of microprolactinomas. STUDY TYPE: Prospective. POPULATION: Thirty-four patients in microprolactinomas with high signal on T2WI (HT2-PRL) group (34 females, 34 ± 7 years), 26 patients in microprolactinomas with equal or low signal on T2WI (ELT2-PRL) group (21 females, 34 ± 7 years), 35 patients with hyperprolactinemia (33 females, 32 ± 8 years), and 30 normal controls (25 females, 31 ± 7 years). FIELD STRENGTH/SEQUENCE: TSE sequence at 3 T. ASSESSMENT: Pituitary morphological parameters (such as length and volume), dynamic contrast-enhanced parameters (such as time to peak) and the apparent diffusion coefficients (ADCs) were measured in each group. STATISTICAL TESTS: ANOVA and Mann-Whitney U test were used to compare parameters among groups. Spearman's coefficient was used to evaluate the correlation between variables. ROC analysis was used to assess the performance of the parameters. A P-value <0.05 was considered statistically significant. RESULTS: The pituitary volume of patients in HT2-PRL, ELT2-PRL, and hyperprolactinemia group were 831.00 (747.60, 887.60), 923.63 ± 219.34, and 737.20 (606.40, 836.80) mm3. The pituitary maximum height in these three groups were 7.03 (6.43, 8.63), 8.03 ± 1.41, and 6.63 ± 1.28 mm, respectively. The lesion ADC value was significantly correlated with T2 relative signal intensity (the ratio of signal intensity of microprolactinoma or anterior pituitary to left temporal cortex) (r = 0.821). Compared with patients with hyperprolactinemia, the diagnostic efficacy of T2 relative signal intensity was higher in HT2-PRL group, with an AUC of 0.954, whereas the ADC value was the highest in ELT2-PRL group, with an AUC of 0.924. CONCLUSION: DWI sequences can be used to assist in the diagnosis of pituitary microadenomas. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
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Disturbance of neurovascular coupling (NVC) is suggested to be one potential mechanism in type 2 diabetes mellitus (T2DM) associated mild cognitive impairment (MCI). However, NVC evidence derived from functional magnetic resonance imaging ignores the relationship of neuronal activity with vascular injury. Twenty-seven T2DM patients without MCI and thirty healthy controls were prospectively enrolled. Brain regions with changed susceptibility detected by quantitative susceptibility mapping (QSM) were used as seeds for functional connectivity (FC) analysis. NVC coefficients were estimated using combined degree centrality (DC) with susceptibility or cerebral blood flow (CBF). Partial correlations between neuroimaging indicators and cognitive decline were investigated. In T2DM group, higher susceptibility values in right hippocampal gyrus (R.PHG) were found and were negatively correlated with Naming Ability of Montreal Cognitive Assessment. FC increased remarkably between R.PHG and right middle temporal gyrus (R.MTG), right calcarine gyrus (R.CAL). Both NVC coefficients (DC-QSM and DC-CBF) reduced in R.PHG and increased in R.MTG and R.CAL. Both NVC coefficients in R.PHG and R.MTG increased with the improvement of cognitive ability, especially for executive function. These demonstrated that QSM and DC-QSM coefficients can be promising biomarkers for early evaluation of cognitive decline in T2DM patients and help to better understand the mechanism of NVC.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Encéfalo , Disfunção Cognitiva/patologia , Cognição/fisiologia , Lobo Temporal , Imageamento por Ressonância Magnética/métodosRESUMO
A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.
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Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Estudos de Coortes , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Súbita/diagnóstico por imagem , Perda Auditiva Súbita/complicações , Perda Auditiva Súbita/terapia , Audição , Neuroimagem , Estudos RetrospectivosRESUMO
Large conductance Ca2+-activated potassium (BKCa) channels are regulated by intracellular free Ca2+ concentrations ([Ca2+]i) and channel protein phosphorylation. In hypercholesterolemia (HC), motility impairment of the sphincter of Oddi (SO) is associated with abnormal [Ca2+]i accumulation in smooth muscle cells of the rabbit SO (RSOSMCs), which is closely related to BKCa channel activity. However, the underlying mechanisms regulating channel activity remain unclear. In this study, an HC rabbit model was generated and used to investigate BKCa channel activity of RSOSMCs via SO muscle tone measurement in vitro and manometry in vivo, electrophysiological recording, intracellular calcium measurement, and Western blot analyses. BKCa channel activity was decreased, which correlated with [Ca2+]i overload and reduced tyrosine phosphorylation of the BKCa α-subunit in the HC group. The abnormal [Ca2+]i accumulation and decreased BKCa channel activity were partially restored by Na3VO4 pretreatment but worsened by genistein in RSOSMCs in the HC group. This study suggests that α-subunit tyrosine phosphorylation is required for [Ca2+]i to activate BKCa channels, and there is a negative feedback between the BKCa channel and the L-type voltage-dependent Ca2+ channel that regulates [Ca2+]i. This study provides direct evidence that tyrosine phosphorylation of BKCa α-subunits is required for [Ca2+]i to activate BKCa channels in RSOSMCs, which may be the underlying physiological and pathologic mechanism regulating the activity of BKCa channels in SO cells.
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Canais de Potássio , Esfíncter da Ampola Hepatopancreática , Animais , Coelhos , Fosforilação , Processamento de Proteína Pós-Traducional , TirosinaRESUMO
Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
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Alquil e Aril Transferases , Cinnamomum camphora , Cinnamomum camphora/enzimologia , Alquil e Aril Transferases/químicaRESUMO
Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3) is a crucial oncogene in human lung cancer, whereas protein kinase C δ (PKCδ) acts as a tumor suppressor. In this study, we aimed to explore the regulation by PLOD3 on the expression of YAP1 to affect the progression of non-small cell lung cancer (NSCLC) via the PKCδ/CDK1/LIMD1 signaling pathway. We found that PLOD3, CDK1, and YAP1 were highly expressed, while LIMD1 was poorly expressed in NSCLC tissues. Mechanistic investigation demonstrated that silencing PLOD3 promoted the cleavage of PKCδ in a caspase-dependent manner to generate a catalytically active fragment cleaved PKCδ, enhanced phosphorylation levels of CDK1, and LIMD1 but suppressed nuclear translocation of YAP1. Furthermore, functional experimental results suggested that loss of PLOD3 led to increased phosphorylation levels of CDK1 and LIMD1 and downregulated YAP1, thereby suppressing the proliferation, colony formation, cell cycle entry, and resistance to apoptosis of NSCLC cells in vitro and inhibiting tumor growth in vivo. Taken together, these results show that PLOD3 silencing activates the PKCδ/CDK1/LIMD1 signaling pathway to prevent the progression of NSCLC, thus providing novel insight into molecular targets for treating NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Apoptose , Proteína Quinase CDC2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM , Neoplasias Pulmonares/metabolismo , Transdução de Sinais , Proteínas de Sinalização YAPRESUMO
BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.
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Fenda Labial , Fissura Palatina , Hepatite B Crônica , Hepatite B , Feminino , Humanos , Gravidez , Recém-Nascido , Adulto , Antígenos de Superfície da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Gestantes , Estudos Prospectivos , Fenda Labial/induzido quimicamente , Fenda Labial/tratamento farmacológico , Fissura Palatina/induzido quimicamente , Fissura Palatina/tratamento farmacológico , Tenofovir/efeitos adversos , Adenina/efeitos adversos , China , Antivirais/efeitos adversos , Hepatite B/diagnósticoRESUMO
Owing to the limitations of cross-sectional studies, it is unclear whether social media induce brain changes, or if individuals with certain biological traits are more likely to use social media. Functional connectivity (FC) can reflect cerebral functional plasticity, and if social media can influence cerebral FC, then the FC of light social media users should be more similar to that of heavy users after they "heavily" used social media for a long period. We combined longitudinal study design and intersubject correlation (ISC) analysis to investigate this similarity. Thirty-five heavy and 21 light social media users underwent cognitive tests and functional MRIs. The 21 light social media users underwent another functional MRI scan after completing an additional four-week social media task. We conducted the ISC at the group, individual, and brain-region levels to investigate the similarity of FC and locate the brain regions most affected by social media. The FC of light social media users was more similar to that of heavy social media users after they completed the four-week social media task. Then, social media had an impact on half of the brain, involving almost all brain networks. Finally, cerebral FC that mostly affected by social media was associated with selective attention. We concluded that the impact of social media use on cerebral functional connectivity changes is revealed by ISC method and longitudinal design, which may provide guidance for clinical practice. The methods used in the current research could also be applied to similar domains.
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Mídias Sociais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Estudos Transversais , Humanos , Estudos Longitudinais , Imageamento por Ressonância MagnéticaRESUMO
Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.
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Hepatite C Crônica , Sofosbuvir , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/genética , Humanos , Recém-Nascido , Gravidez , Gestantes , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
Thymic lymphoepithelioma-like carcinoma (LELC) is a rare primary malignant neoplasm originating from the thymus. Thymic LELC diagnosis is often terminal when diagnosed, some patients have lost the opportunity for surgery. Platinum- and anthracycline-based systemic chemotherapy are the first-line treatment plan; however, there is no clear consensus on therapy when first-line treatment fails because of the lack of cases of advanced thymic LELC. Here was a rare case of advanced thymic LELC with bone marrow metastasis at relapse, which is reported in a patient who responded well to toripalimab combined with anlotinib therapy. The treatment showed tolerable toxicity with good antitumor activity in the patient. As far as we know, this is the first case that the combination of toripalimab with anlotinib is effective in controlling advanced thymic LELC with bone marrow metastasis. The case reports represent an essential means by which an effective therapy for advanced thymic LELC may not be practical given the low frequency of a thymic LELC with multiple metastases.
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Neoplasias da Medula Óssea , Neoplasias Ósseas , Carcinoma de Células Escamosas , Humanos , Imunoterapia , PlatinaRESUMO
OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: ⢠Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. ⢠The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. ⢠The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.
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Linfoma , Timoma , Neoplasias do Timo , Colágeno , Imagem de Difusão por Ressonância Magnética , Humanos , Linfoma/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagemRESUMO
PURPOSE: This study aimed to investigate the value of magnetic resonance (MR) characteristics in differentiating the subtypes of growth hormone pituitary adenomas. MATERIALS AND METHODS: The clinical and MR imaging data of 70 patients with growth hormone pituitary adenoma confirmed by surgery and pathology were retrospectively analyzed. The tumors were divided into dense granular (DG; 36 cases) and sparse granular subtypes (SG; 34 cases). The tumors' MR features were analyzed, including the mean and maximum diameters, T2 signal intensity, T2 relative signal intensity (rSI), homogeneity, enhancement degree, and invasiveness (Knosp grade). Mann-Whitney U test and χ2 test were used to analyze MR characteristics between the 2 groups. The independent predictors and predictive probabilities of tumor subtypes were obtained via a logistic regression model, and the efficacy was compared by receiver operating characteristic curve. RESULTS: The mean and maximum diameters of growth hormone adenoma in DG and SG were 1.77 versus 2.45 and 1.95 versus 3.00 cm (median, P < 0.05), respectively. There was a significant difference between the 2 groups in T2 signal intensity and rSI (P values were 0.02 and 0.001, respectively). Most DG adenomas (86.1%) appeared as hypointense on T2 images, and 38.2% of SG adenomas were hyperintense. There was no significant difference in tumor homogeneity (P = 0.622). A significant difference was found in the Knosp grade between the 2 subtypes (P = 0.004). In addition, the enhancement degree of SG adenomas was significantly higher than that of DG adenomas (P = 0.001). Logistic regression analysis showed that high T2 rSI value and marked contrast enhancement were independent predictors of the 2 subtypes, and the odds ratios were 4.811 and 4.649, respectively. The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve, sensitivity, and specificity were 0.765, 0.882, and 0.500, respectively. CONCLUSIONS: There are significant differences in tumor size, T2 signal intensity, T2 rSI, enhancement degree, and invasiveness between DG and SG adenomas. The logistic model based on the marked contrast enhancement and high T2 rSI value has an important value in predicting the subtype of growth hormone adenoma.
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Adenoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/diagnóstico por imagem , Adenoma/classificação , Adenoma/patologia , Adulto , Feminino , Hormônio do Crescimento/sangue , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200â 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.
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Hepatite B Crônica , Hepatite B , Complicações Infecciosas na Gravidez , Alanina , Antivirais/efeitos adversos , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Prospectivos , Tenofovir/análogos & derivados , Carga ViralRESUMO
OBJECTIVES: Accurately predicting the WHO classification of thymomas is urgently needed to optimize individualized therapeutic strategies. We aimed to develop and validate a combined radiomics nomogram for personalized prediction of histologic subtypes in patients with thymomas. METHODS: A total of 182 thymoma patients were divided into training (n = 128) and test (n = 54) cohorts. Radiomics features were extracted from T2-weighted, T2-weighted fat suppression, and diffusion-weighted images to establish a radiomics signature in the training cohort. Multivariate logistic regression analysis was used to develop a combined radiomics nomogram that incorporated clinical, conventional MR imaging variables, apparent diffusion coefficient (ADC) value, and radiomics signature. The efficacy of clinical, conventional MR imaging, or ADC model was also evaluated respectively. The performances of different models were compared by receiver operating characteristic analysis and Delong test. The discrimination, calibration, and clinical usefulness of the combined radiomics nomogram were assessed. RESULTS: The radiomics signature, consisting of 14 features, achieved favorable predictive efficacy in differentiating low-risk from high-risk thymomas, outperforming clinical, conventional MR imaging, and ADC models. The combined radiomics nomogram incorporating tumor shape, ADC value, and radiomics signature yielded the best performance (training cohort: area under the curve [AUC] = 0.946, test cohort: AUC = 0.878). The calibration curve and decision curve analysis indicated the clinical utility of the combined radiomics nomogram. CONCLUSIONS: The radiomics signature is a useful tool that can be used to predict histologic subtypes of thymomas. The combined radiomics nomogram improved the individualized subtype prediction in patients with thymomas. KEY POINTS: ⢠Fourteen robust features were selected to develop a radiomics signature for preoperative prediction of thymoma subtype. ⢠MRI-based radiomics signature can differentiate low-risk thymomas from high-risk thymomas with favorable predictive efficacy compared with clinical, conventional MR imaging, and ADC models. ⢠Combined radiomics nomogram based on tumor shape, ADC value, and radiomics signature could improve the individualized subtype prediction in patients with thymomas.
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Timoma , Neoplasias do Timo , Humanos , Imageamento por Ressonância Magnética , Nomogramas , Estudos Retrospectivos , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagemRESUMO
BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.
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COVID-19/complicações , Fígado/virologia , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Feminino , Humanos , Fígado/patologia , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.
Assuntos
COVID-19/complicações , Ecocardiografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , COVID-19/diagnóstico , Estado Terminal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T1-weighted contrast enhanced imaging(T1CE) in differentiating pseudoprogression from true progression after standard treatment for GBM. METHODS: Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T1CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T1CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity. RESULTS: No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists' assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively. CONCLUSION: T1CE-based radiomics showed better classification performance compared with radiologists' assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/terapia , Meios de Contraste , Progressão da Doença , Feminino , Glioblastoma/terapia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Doses de Radiação , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Social capital has been linked to health behaviours, but the underlying mechanism is unclear. Previous studies have found that health literacy played the role of a mediator in the relationships among social capital, individual physical activity and nutrition. But it is not clear whether eHealth literacy mediates the impact of social capital on health behaviours. Therefore, our research aimed to explore the relationships among social capital (structural and cognitive social capital), eHealth literacy, and the health behaviours of elderly people, and to analyse the mediating effect of eHealth literacy, while providing a theoretical basis for a health behaviour intervention for elderly people. METHODS: From January to February 2019, we conducted a cross-sectional survey of 1201 Chinese people aged over 60 years using the Chinese Shortened Social Capital Scale (contains two subscales of structural social capital and cognitive social capital), eHealth Literacy Scale, and Health-Promoting Lifestyle Profile. We used structural equation modelling to test a hypothetical mediation model. RESULTS: The mean scores of social capital was 72.07 (SD = 13.03), 17.24 (SD = 9.34) for eHealth literacy, and 112.23 (SD = 23.25) for health behaviours. Social capital and eHealth literacy were significantly correlated with health behaviours, and social capital and structural social capital were significantly correlated with eHealth literacy. Lastly, eHealth literacy mediated the relationship between structural social capital and health behaviours. CONCLUSIONS: eHealth literacy was an important mediating factor for elderly people's structural social capital and health behaviours. Therefore, social capital and eHealth literacy must be considered when designing and implementing health behaviour intervention programmes for elderly people.
Assuntos
Letramento em Saúde , Capital Social , Telemedicina , Idoso , China , Estudos Transversais , Comportamentos Relacionados com a Saúde , Humanos , Inquéritos e QuestionáriosRESUMO
Viscum articulatum Burm. f. is a parasitic plant rich in flavonoids, triterpenoids, and catechins and has a high nutritional value. It has been reported that consuming V. articulatum can prevent cardiac diseases. In this study, six bioactive compounds, including catechins, triterpenoids, and phenylpropanoid glycosides, were determined in alcohol extracts of the plant using HPLC. The anti-inflammatory and antioxidant activities of three catechins, two triterpenoids, and three combination drugs were measured in cardiomyocytes, and the results showed that the anti-inflammatory activity was significantly enhanced while retaining strong antioxidant activity when epicatechin and ursolic acid were used in combination. The main quality markers epicatechin and ursolic acid were screened based on the specificity of the genuine herb and a potent synergistic effect, and the lowest limitation contents of V. articulatum which could discriminate it from some other taxonomically similar materials were accordingly determined. This self-built lowest limitation content of the two screened quality markers could quickly and accurately reflect the efficacy in terms of chemical composition and reverse the disorderly market use of nongenuine herbs or confusing species for adulteration. This study is of some significance for market regulation, drug development, and clinical medication.