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In recent years, PD-1/PD-L1 checkpoint blockade immunotherapy with remarkable efficacy has set off a heat wave. The expression level of PD-L1, which plays a predictive role in anti-PD-1/PD-L1 therapy, could be quantified by noninvasive imaging with radiotracers. Herein, we introduced the synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule radiotracer [99mTc]G3C-CBM for PD-L1 imaging. [99mTc]G3C-CBM was achieved with high radiochemical purity (>96 %) and remained good stability in PBS and FBS. In competitive combination experiment, [99mTc]G3C-CBM was displaced by increasing concentrations of unlabeled G3C-CBM, resulting in an IC50 value of 41.25±2.23 nM for G3C-CBM. The uptake of [99mTc]G3C-CBM in A375-hPD-L1 cells (17.51±2.08 %) was approximately 6.47 folds of that in A375 cells (2.71±0.36 %) after co-incubation for 2 h. The biodistribution results showed that the radioactivity uptake in A375-hPD-L1 tumor reached the maximum (0.35±0.01 %ID/g) at 2 h post injection, and the optimum tumor/muscle ratio of 2.94±0.29 occurred at the same time. In addition, [99mTc]G3C-CBM was quickly cleared from the blood with a clearance half-life of just 119.25 min. These results indicate that [99mTc]G3C-CBM is a potential SPECT PD-L1 imaging agent and is worthy of further study.
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Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Transporte BiológicoRESUMO
Cerebral revascularization is the ultimate treatment for a subset of complex middle cerebral artery (MCA) aneurysms. The decision for the revascularization strategy should be made during the treatment process. This study aimed to summarize the revascularization strategies for different types of complex MCA aneurysms and their outcomes. The clinical data of patients with complex MCA aneurysms who underwent cerebral revascularization since 2015 were analyzed retrospectively. The aneurysms were classified according to the location and other main characteristics that affect the selection of surgical modalities. The corresponding surgical modalities and treatment outcomes were summarized. A total of 29 patients with 29 complex MCA aneurysms were treated with cerebral revascularization from 2015 to 2022. Treated aneurysms were located at the prebifurcation segment in 7 patients, bifurcation segment in 12 patients, and postbifurcation segment in 10 patients. Surgical modalities in the prebifurcation segment included four high-flow extracranial-to-intracranial (EC-IC) bypasses with aneurysm trapping or proximal occlusion, two IC-IC bypasses with aneurysm excision, and one combination bypass with aneurysm excision. In the bifurcation segment, surgical modalities included two low-flow EC-IC bypasses with aneurysm excision or trapping, six IC-IC bypasses with aneurysm excision, three combination bypasses with aneurysm excision, and one constructive clipping with IC-IC bypass. In the postbifurcation segment, surgical modalities included nine IC-IC bypasses with aneurysm excision and low-flow EC-IC bypass with aneurysm trapping. The revascularization strategy for prebifurcation aneurysms was determined based on the involvement of lenticulostriate arteries, whereas the strategy for bifurcation aneurysms was determined based on the number of distal bifurcations and the shape of the aneurysm. The location of the aneurysm determined the revascularization strategy for aneurysms in the postbifurcation segments. Angiography demonstrated that aneurysms were completely obliterated in 26 cases and shrank in 3 cases, and all bypasses except one were patent. The mean follow-up period was 47.5 months. Three patients developed hemiplegic paralysis, and one developed transient aphasia postoperatively due to cerebral ischemia. No new neurological dysfunction occurred in the other 25 patients with no recurrence or enlargement of aneurysms during the follow-up. Prebifurcation aneurysms involving the lenticulostriate arteries require proximal occlusion with high-flow bypass. Most of the other aneurysms can be safely excised or trapped by appropriate revascularization strategies according to their location and orientation.
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Revascularização Cerebral , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Neurocirúrgicos , Artéria Cerebral Média/cirurgiaRESUMO
Orobanche caerulescens is an important medicinal resource in Orobanchaceae. The present study aims to establish methods for determination of acteoside, crenatoside, and total phenylethanoid glycosides in O. caerulescens, and determine the content in 15 samples to evaluate the resource utilization of this medicinal plant. The content of acteoside and crenatoside were quantitatively determined by HPLC, while total phenylpropanoid glycosides was estimated by UV-VIS spectrophotometry. According to the results, the content of acteoside was the highest in O. caerulescens, followed by crenatoside. The contents of acteoside, crenatoside, and total phenylethanoid glycosides were between 1.15% - 15.60%, 0.83% - 4.47%, and 6.78% - 27.43%, respectively, which had significant differences. The acquisition time has great influence on the content of main components of O. caerulescens. The content of phenylethanoid glycosides is higher in the samples which were collected at the flowering stage. The two determination methods were proved to be simple, accurate and reliable, and can be used to evaluate the quality and resource utilization of O. caerulescens.
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Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Orobanche/químicaRESUMO
On 7 December 2022, the State Council of China released 'Measures to Further Optimize the Implementation of the Prevention and Control of the New Coronavirus Epidemic'. The previous three-year dynamic zero epidemic prevention policy was then replaced with a full liberalization policy. On 5 May 2023, the World Health Organization declared that COVID-19 no longer constituted a 'public health emergency of international concern.' However, given the ongoing prevalence of coronavirus, emerging mutations, and the liberalization of restrictions, there are increased risks of vulnerable people contracting new variants. Low vaccination coverage among older people with compromised immune systems, puts them at further risk. The policy shift will increase pressure on already stretched health infrastructure and medical resources. This short article adds to the current debate arguing that the Chinese government should take commensurate preventive measures, including strengthening medical facilities and equipment and targeting ongoing vaccination in older people.
Paper ContextThe COVID-19 pandemic has disproportionately affected older people.This short paper discusses the consequences of China's liberalization policy on the older population.It suggests that the Chinese government should have taken targeted measures to mitigate health risks occurring under the changed circumstances.
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COVID-19 , Política de Saúde , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Idoso , Saúde Pública , Vacinas contra COVID-19/administração & dosagemRESUMO
Objectives: The aims of this study were to screen for phagocytosis regulator-related genes in tissue samples from children with medulloblastoma (MB) and to construct a prognostic model based on those genes. Methods: Differentially expressed genes between the MB and control groups were identified using the GSE50161 dataset from the Gene Expression Omnibus database. Prognosis-related phagocytosis regulator genes were selected from the GSE85217 dataset. Intersecting genes of the two datasets (differentially expressed prognosis-related phagocytosis regulator genes) were submitted to unsupervised cluster analysis to identify disease subtypes, after which the association between the subtypes and the immune microenvironment was analyzed. A prognostic risk score model was constructed, and functional, immune-related, and drug sensitivity analyses were performed. Results: In total, 23 differentially expressed prognosis-related phagocytosis regulator genes were identified, from which two disease subtypes (clusters 1 and 2) were classified. The prognoses of the patients in cluster 2 were significantly worse than those of the patients in cluster 1. The immune microenvironment differed significantly between the two subtypes. Finally, 10 genes (FAM81A, EZR, NDUFB9, RCOR1, FOXO4, NHLRC2, KIF23, PTPN6, SMAGP, and MED13) were selected to establish the prognostic risk score model. The prognosis in the low-risk group was better than that in the high-risk group. The model genes NDUFB9 and PTPN6 were positively correlated with M2 macrophages. Conclusion: Ten key phagocytosis regulator genes were screened to construct a prognostic model for MB. These genes may serve as key biomarkers for predicting the prognosis of patients with this type of brain cancer.
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BACKGROUND AND PURPOSE: To examine the diagnostic value of imaging features in cavernous sinus hemangioma (CSH). MATERIALS AND METHODS: The clinical and imaging data of patients with pathologically confirmed CSH, cavernous sinus meningioma, trigeminal schwannoma and pituitary adenoma invading the cavernous sinus between May 2017 and May 2022 were retrospectively analyzed. The cases were divided into the CSH and non-CSH groups to summarize the magnetic resonance imaging (MRI) characteristics of CSH. Univariate χ2 analysis was performed to assess five indexes, including signal intensity on T2WI, homogeneity of T2WI, enhancement of enhanced T1, enhanced T1 with dural tail sign, and cavernous sinus swelling and extrusion sign. RESULTS: There were significant differences in four features, including hyperintensity on T2WI, homogeneity of T2WI, T1-enhanced without meningeal tail sign, and cavernous sinus swelling and extrusion sign between the CSH and non-CSH groups, with cavernous sinus swelling and extrusion sign showing the most pronounced distinction, with a sensitivity of 100%, a specificity of 93.02%, and an accuracy of 94.23%. The four features could be jointly used as diagnostic criteria, with a sensitivity of 94.44%, a specificity of 100.00%, and an accuracy of 99.04%. CONCLUSION: Cavernous sinus swelling and extrusion sign is a reliable imaging index for CSH diagnosis. Homogenous hyperintensity or marked hyperintensity on T2WI, enhanced T1 without dural tail sign, and cavernous sinus swelling and extrusion sign could be jointly used as diagnostic criteria, which may improve the accuracy of CSH diagnosis.
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Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings.
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Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.
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Primary suprasellar germinoma (PSG) is a rare malignant tumor of the central nervous system. This study aimed to explore the clinical characteristics, treatment protocol, and prognosis of patients with PSG. This case series retrospectively analyzed the clinical data of patients with PSG in Tianjin Huanhu Hospital diagnosed between January 2016 and December 2021. Fifteen patients with an average age of 19.6 years were included, in which nine of them were males. The mean duration between initial symptoms and admission was 17.0 months. The mean follow-up was 40.8 months. Ten patients had polydipsia and polyuria, visual impairments were observed in 8 patients, and 2 cases (13.3%) had symptoms both from suprasellar and pineal regions. All 15 cases were histopathologically confirmed as germinoma through craniotomy or biopsy. Most patients (80%) underwent radiotherapy combined with chemotherapy. During follow-up, all the patients showed a reduction in tumor size, especially in the bifocal cases. Symptoms of polydipsia, polyuria, and visual impairment were markedly relieved to different degrees. All patients had recovered well at discharge. Patients with polydipsia and polyuria took desmopressin daily. A histological confirmation by open biopsy through craniotomy or endoscopic biopsy might be recommended for PSG to start the appropriate treatments. Patients with PSG will usually have a good prognosis, but attention should be paid to the treatment of endocrine deficiencies.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Germinoma , Neoplasias de Cabeça e Pescoço , Masculino , Humanos , Adulto Jovem , Adulto , Feminino , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Estudos Retrospectivos , Poliúria , Germinoma/complicações , Germinoma/diagnóstico , Germinoma/terapiaRESUMO
BACKGROUND AND OBJECTIVES: Spinal deformities are a common complication after selective dorsal rhizotomy (SDR). In this article, we introduce a more minimally invasive SDR procedure in adult patients with spastic paralysis of the lower limbs. METHODS: In this retrospective analysis of SDR in 8 adult patients with spastic paralysis of the lower limbs, a modified exposure method was used during the surgery. Only the lower part of the L1 spinous process, upper part of the L2 spinous process, and part of the lamina were resected through L1-2 interlaminar approaches. The motor and sensory roots were found to be completely dependent on electrophysiological monitoring. The sensory roots of the target muscle groups were partially transected. All patients were followed up for 2-4 years. The degree of lower extremity spasm was assessed using the Gross Motor Function Classification Scale, Ashworth grading, Gross Motor Function Measure-66, joint range of motion, and electromyography analysis. RESULTS: All 8 patients were successfully operated with the help of intraoperative electrophysiological monitoring. The Ashworth score of the target muscles, Gross Motor Function Measure-66 score, and range of motion of the joints improved significantly after surgery. Two patients achieved cross-grade improvement in their Gross Motor Function Classification Scale scores. No persistent incision pain or spinal deformities were observed during follow-up. CONCLUSION: The interspinous process approach provides sufficient surgical space and reduced the damage to the bone structure of the spine. The electrophysiological monitoring protocol is suitable for adult patients with lower extremity spasm.
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Polymer flooding is an effective enhanced oil recovery (EOR) technology used in Daqing Oilfield. Microscopic distribution of remaining oil in polymer-flooded reservoirs is more complicated in comparison with waterflooded reservoirs. In this paper, UV excitation, frozen section-laser confocal technology, and three-dimensional reconstruction technology were employed to investigate the distribution law and occurrence state of the microscopic remaining oil in polymer-flooded Daqing Oilfield. With these methods, the occurrence states of the microscopic remaining oil distribution in different washing degrees and displacement locations were analyzed, and the remaining oil distribution before and after polymer flooding was compared quantitatively. The changes and microscopic distribution characteristics of crude oil components in the process of polymer flooding were clarified, and the relationship between clay minerals and the microscopic remaining oil distribution was discussed. Based on the statistical analysis of experimental results, the remaining oil of the free state decreases gradually, while the remaining oil of the bound state increases as the washing degree increases. In addition, the remaining oil in the distributary line is more enriched than the mainstream line after polymer flooding. Compared with waterflooding, the remaining oil of the free state becomes more, while the remaining oil of the bound state becomes less after polymer flooding. The frozen section-laser confocal experimental results also indicate that the proportion and distribution characteristics of the remaining oil components have been changed, and heavy components increase while light components decrease in the polymer-flooded stage. This research performs the quantized characterization and detailed analysis of remaining oil systematically and lays the foundation for remaining oil prediction and potential tapping in polymer-flooded reservoirs.
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This work focuses on the two-phase slug flow in the curve pipe, which is very common in oil/gas wells. In terms of oil and gas production, the unstable slug flow may cause several problems and reduce production. In the present work, slug flow experiments were conducted in several curve pipes for varying inflow angles and gas-liquid velocity ratios. The real-time pressure was measured at the curve pipe using the Rosemount pressure gauges, and the liquid holdup was measured using the conductivity sensors, which were used to calculate the slug length. Then, we define the dimensionless slug length φD = L S/D (the ratio of slug length L to pipe diameter D), which can make the slug analysis free from the influence of different pipe diameters; φD is also used to analyze the change in the slug flow state. The experimental results show that the dimensionless slug length φD increases with the increase in the pipe curvature; φD first decreases and then increases with the increase in the inflow angle; φD also increases with the increase in the gas-liquid velocity ratio. This study adopts a dynamic slug flow model to simulate the well completion and the throttle cases under field conditions based on the hydraulic similarity principle. The pressure and liquid holdup results show that the large-scale segregated completion will lead to decreasing flow instability and the decrease in throttle opening will also lead to the decrease in flow instability.
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It has been a great challenge for the oil and gas industry to timely identify any electrical submersible pump (ESP) abnormal performance to avoid ESP failure. Given the high cost of the ESP failure, more and more real-time surveillance systems are applied to monitor ESP performance to generate alarms in the case of failures. This paper presents a robust principal component analysis (PCA) model to perform fault detection for ESP systems continuously. A three-dimensional plot of scores of principal components was used to observe different patterns during the stable and failure periods. 47 cases of actual failure events and 40 cases of stable operating events were tested on the robust PCA model to generate prediction results. The testing results demonstrate that the robust PCA model has managed to identify 20 failure events before the actual failure time out of the 47 failure cases and has successfully distinguished all the 40 stable operating wells. This study has concluded that PCA has the potential to be used as a monitoring platform to recognize dynamic change and therefore to predict the developing failures in the ESP system.
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Aflatoxins are the most toxic type of mycotoxins, which may cause serious carcinogenesis, teratogenesis, and mutagenesis to humans and animals. In this work, we demonstrate a novel label-free fluorescent aptasensor based on exonuclease-assisted triple recycling amplification for the sensitive detection of aflatoxin B1 (AFB1). With the close cooperation of T7 exonuclease and three elaborately designed hairpin probes, the target AFB1 can perform three consecutive cycles of amplification reactions. In this process, each hairpin probe is fully utilized, and the target AFB1, the secondary target and the tertiary target are recycled, thereby achieving a high amplification. Interestingly and importantly, the secondary and tertiary targets generated by amplification are also excellent DNA template sequences for silver nanoclusters (AgNCs). In the presence of NaBH4 and AgNO3, a great number of DNA-AgNCs are synthesized, thereby producing a strong fluorescent signal. Under optimal conditions, the developed aptasensor exhibited high sensitivity to AFB1 with a low detection limit of 0.19 pg mL-1 and a wide dynamic range of 1 × 10-6-1 µg mL-1. In addition, the aptasensor also performed well in the determination of AFB1 in real samples.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Aflatoxina B1/análise , DNA , Humanos , Limite de Detecção , PrataRESUMO
Trilinear flow model is an effective method to reproduce the flow behavior for horizontal wells with multistage hydraulic fracture treatments in unconventional reservoirs. However, models developed so far for transient analysis have rarely considered the inflow performance of wells. This paper introduces a new composite dual-porosity trilinear flow model for the multiple-fractured horizontal well in the naturally fractured reservoirs. The analytical solution is derived under a constant rate condition for analyzing transient pressure behaviors and generating the transient inflow performance relationships (IPRs). The plots of pressure profiles with time could provide insightful information about various flow regimes that develop throughout the entire production cycle. Sensitivity analysis of pressure and pressure derivative response was also performed by varying different parameters (such as hydraulic fracture width and permeability, reservoir configurations, etc.) and by which the impacts of different parameters on the durations of regimes as well as the productivity index can be confirmed. The main outcomes obtained from this study are as follows: (1) the ability to characterize naturally fractured reservoirs using a new composite dual-porosity trilinear flow model; (2) the application of analytical solutions of transient analysis to generate transient IPR curves for different flow regimes; (3) understanding the effect of reservoir configurations, fractures, and matrix characteristics on pressure distribution, flow regime duration, and transient IPR. More specifically, the pressure drop increases and the productivity index decreases with the decrease of the hydraulic fracture conductivity and the increase of matrix permeability and the skin factor. Also, the larger hydraulic fracture spacing and drainage area result in the later onset of the pseudo-steady-state regime. (4) A comprehensive study on transient pressure behaviors and transient inflow performance can provide valuable information to characterize the multifractured complex systems as well as some insights into the production.
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Malathion is one of the most commonly used organophosphorus pesticides that can cause serious harm to the ecological environment and human health. Herein, we demonstrated a label-free chemiluminescent aptasensor for the sensitive detection of malathion based on exonuclease-assisted dual signal amplification and G-quadruplex/hemin DNAzyme. Upon the addition of malathion, the aptamer probe specifically bound to the target to form a complex malathion-S3, leaving a duplex S1-S2. The complex malathion-S3 was digested by exonuclease I and the target was released. The released target was recycled to perform exonuclease I-assisted signal amplification. Furthermore, after treatment with exonuclease III, the duplex S1-S2 was converted into the secondary target ST. The secondary target ST interacted with the hairpin H1 to form a complex H1-ST, which was further digested by exonuclease III and released the secondary target. The released secondary target was recycled to perform exonuclease III-assisted signal amplification. After complete amplification, large numbers of G-quadruplex/hemin DNAzymes were generated. Under the optimal experimental conditions, the prepared aptasensor showed an excellent linear response to malathion with a detection limit of 0.47 pM. The relative standard deviations were in the range of 4.2-6.9%. Moreover, the aptasensor was successfully applied to detect malathion in spiked food and traditional Chinese medicine samples.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , Hemina , Humanos , Limite de Detecção , Luminescência , MalationRESUMO
BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA), a natural component of bile, has been synthesized to treat cholestatic liver diseases such as primary biliary cirrhosis. Broad biochemical changes in UDCA-treated patients suggest beneficial effects of UDCA beyond stimulating hepatobiliary secretion and possible efficacy of the medicine in treating cirrhosis of other causes. The aim was to explore the potential benefit of UDCA in controlling immune-mediated hepatic fibrosis. METHODOLOGY: We applied the rat experimental model of liver fibrosis induced by intraperitoneal injection of porcine serum. UDCA was administered orally during the course of the serum injections. RESULTS: Compared with the untreated group, the rats treated with UDCA ended with significantly higher body weight, lower liver weight, and lower spleen weight. The treated groups also demonstrated less severe liver fibrosis, with significantly lowered hepatic expression of type I and type III collagens, in terms of both mRNA and proteins. Moreover, serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (C IV), and type III procollagen (PC III) were also lower in the UDCA-treated animals. CONCLUSION: UDCA deters development of immune-mediated liver fibrosis by inhibiting the expression of collagen and other extracelluar matrix components.
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Cirrose Hepática Experimental/prevenção & controle , Ácido Ursodesoxicólico/uso terapêutico , Animais , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Feminino , Fígado/patologia , Fígado/ultraestrutura , Cirrose Hepática Experimental/imunologia , Cirrose Hepática Experimental/patologia , Masculino , Microscopia Eletrônica , Ratos , Ratos Wistar , SuínosRESUMO
Angiocentric glioma (AG) is a rare subtype of neuroepithelial tumor in children and young adults that commonly presents with seizures. To study the clinical characteristics, treatment and prognosis of patients with AG, the features of two cases of AG were described and 108 cases reported in the literature were assessed. The cases of the present study were two males aged 8 and 16 years, who mainly presented with seizures. MRI revealed superficial, non-enhanced lesions in the left temporal and right frontal lobe, respectively. The two patients underwent gross total resection (GTR) and remained seizure-free without neurological deficits after 3.5 and 2.5 years, respectively. Histopathological examination revealed that the tumors consisted of monomorphous cells that surrounded the blood vessels and neurons in the cerebral cortex, and formed concentric sleeves or pseudorosettes. Furthermore, immunostaining indicated that the diffuse infiltrative neoplastic cells were positive for glial fibrillary acidic protein and a dot-like pattern of epithelial membrane antigen was observed. AG mostly appeared similar to low-grade gliomas on MRI. GTR of the lesions was curative and radiation or chemotherapy were not required. AG typically has a favorable prognosis, with low mortality and incidence of disability.
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Cerebral cavernous malformations (CCMs) are common vascular malformations in the central nervous system. Familial CCMs (FCCMs) are autosomal dominant inherited disease with incomplete penetrance and variable symptoms. Mutations in the KRIT1, CCM2, and PDCD10 genes cause the development of FCCM. Approximately 476 mutations of three CCM-related genes have been reported, most of which were case reports, and lack of data in stable inheritance. In addition, only a small number of causative missense mutations had been identified in patients. Here, we reported that 8/20 members of a Chinese family were diagnosed with CCMs. By direct DNA sequencing, we found a novel variant c.331G > C (p.A111P) in exon 4 of the CCM2 gene, which was a heterozygous exonic variant, in 7/20 family members. We consider this variant to be causative of disease due to a weaken the protein-protein interaction between KRIT1 and CCM2. In addition, we also found the exon 13 deletion in KRIT1 coexisting with the CCM2 mutation in patient IV-2, and this was inherited from her father (patient III-1H). This study of a Chinese family with a large number of patients with CCMs and stable inheritance of a CCM2 mutation contributes to better understanding the spectrum of gene mutations in CCMs.
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OBJECTIVE: To explore the dynamics of hepatitis B virus covalently closed circular DNA (cccDNA) and optimal duration of treatment after serum virology response. METHODS: HBV cccDNA in liver biopsies and the serum HBV DNA were quantified by real time PCR, the serum makers were detected by enzyme-linked immunosorbent assay. RESULTS: (1) The cccDNA in biopsy samples continued to decrease after serum virology responded. (2) The longer the treatment after serum virology response, the lower the cccDNA level in liver tissue. (3) Anti-HBe positive patients had lower cccDNA in liver tissue than anti-HBe negative patients. (4) cccDNA in liver tissue was undetectable in 12 out of the 18 case anti-HBe(+) patients. Serum virology response lasted 35 months and anti-HBe(+) lasted 30 months. CONCLUSION: After serum virology responded, the longer the treatment, the lower the liver cccDNA. The cccDNA is undetectable in about 2/3 of the patients if the serum virological clearance lasts more than 35 months and anti-HBe lasts more than 30 months.