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1.
Bioorg Med Chem ; 38: 116117, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33838610

RESUMO

Xanthine oxidase is the rate-limiting enzyme critical for the synthesis of uric acid, and therefore xanthine oxidase inhibitors are considered as one of the promising therapies for hyperuricemia and gout. In our previous study, series of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids and 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acids were synthesized that presented excellent in vitro xanthine oxidase inhibitory potency. Interestingly, molecular docking studies revealed that the interaction behavior of these compounds with xanthine oxidase was changed after the conversion from a hydroxy group to amine group. To further investigate the structure-activity relationships of these pyrimidine-containing xanthine oxidase inhibitors and explore the contribution of amino or hydroxy group on xanthine oxidase inhibitory potency, several 2-phenylpyrimidine derivatives with amino or hydroxy functional group were designed and synthesized. Thereafter, the structure-activity research and molecular modeling study proved that hydroxy and amino groups could be used as pharmacophore elements for the design of 2-phenylpyrimidines xanthine oxidase inhibitors. Particularly, the optimized compound, 2-(3-cyano-4-isopentoxy)phenylpyrimidine-4-ol, emerged the strongest xanthine oxidase inhibitor potency, with an IC50 value of 0.046 µM, which was approximately 120-fold more potent than that of allopurinol (IC50 = 5.462 µM). Additionally, Lineweaver-Burk plot analysis revealed that the optimized compound acted as a mixed-type inhibitor. Furthermore, the in vivo hypouricemic effect of the optimized compound was investigated in a hyperuricemia rat model induced by potassium oxonate, and the results showed that the optimized compound could effectively reduce serum uric acid levels at an oral dose of 30 mg/kg.

2.
J Clin Neurosci ; 87: 59-65, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863535

RESUMO

OBJECTIVE: This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. PATIENTS AND METHODS: Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. RESULTS: Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. CONCLUSION: A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

3.
Acta Pharmacol Sin ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742107

RESUMO

Coronavirus disease 2019 (COVID-19) broke out in December 2019. Due its high morbility and mortality, it is necessary to summarize the clinical characteristics of COVID-19 patients to provide more theoretical basis for future treatment. In the current study, we conducted a retrospective analysis of the clinical characteristics of COVID-19 patients and explored the risk factors for the severity of illness. A total of 101 COVID-19 patients hospitalized in Leishenshan Hospital (Wuhan, China) was classified into three sub-types: moderate (n = 47), severe (n = 36), and critical (n = 18); their clinical data were collected from the Electronic Medical Record. We showed that among the 101 COVID-19 patients, the median age was 62 years (IQR 51-74); 50 (49.5%) patients were accompanied by hypertension, while 25 (24.8%) and 22 (21.8%) patients suffered from diabetes and heart diseases, respectively, with complications. All patients were from Wuhan who had a definite history of exposure to the epidemic area. Multivariate logistic regression analysis revealed that older age, diabetes, chronic liver disease, percentage of neutrophils (N%) > 75%, CRP > 4 mg/L, D-dimer > 0.55 mg/L, IL-2R > 710 U/mL, IL-8 > 62 pg/mL, and IL-10 > 9.1 pg/mL were independent variables associated with severe COVID-19. In conclusion, we have identified the independent risk factors for the severity of COVID-19 pneumonia, including older age, diabetes, chronic liver disease, higher levels of N%, CRP, D-dimer, IL-2R, IL-8, and IL-10, providing evidence for more accurate risk prediction.

4.
Eur J Med Chem ; 217: 113359, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33725632

RESUMO

A series of highly active CF3-containing 3'-(nitroisoxazole)spiro[pyrrolidin-3,2'-oxindoles] were synthesized and found to be novel glutathione peroxidase 4 (GPX4)/mouse double minute 2 (MDM2) dual inhibitors. Bioactive spirooxindole and isoxazole skeletons were combined, and the resulting compounds exhibited strong activities against both targets. In particular, compound 3d displayed excellent activity in the suppression of MDM2-mediated degradation of p53, as well as levels of GPX4, in MCF-7 breast cancer cells. Moreover, 3d also exhibited inhibitory effects on MDM2 and GPX4 in MCF-7 xenograft model to trigger ferroptotic and apoptotic cell death in in vivo experiments, which was consistent with the results of in vitro experiments.

5.
J Mol Neurosci ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523385

RESUMO

The 2016 World Health Organization classification of central nervous system tumor firstly introduces molecular diagnosis to glioma, while the molecular features of adult thalamic gliomas (ATGs) in a relatively large sample have not been reported. We aimed at exploring molecular characteristics in ATGs. The data of 97 and 575 newly diagnosed ATGs and superficial gliomas (SGs) patients were collected, and we performed a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: H3 K27M, isocitrate dehydrogenase1 (IDH1), Ki-67, O6-Methylguanine-DNA methyltransferase (MGMT) promoter, EGFR, p53, ATRX, GFAP, Oligo2, PTEN, MGMT, and MMP9 by immunohistochemistry. Direct gene sequencing was performed to test the H3 K27M, IDH1, and TERT promoter mutation. The median age at diagnosis of ATGs was 36.0 years, and majority of them were high-grade glioma. We found a significant difference in H3 K27M mutation (P = 0.003), IDH1 mutation (P < 0.001), MGMT promoter methylation (P = 0.005), and Ki67 > 0.1 (P < 0.001) between ATGs and SGs. The statuses of IDH1 (P < 0.001), MGMT promoter (P < 0.001), and Ki67 (P < 0.001) were significantly different between these two groups in lower-grade gliomas. And statuses of IDH1 (P < 0.001), Ki67 (P < 0.001), and EGFR (P = 0.032) were different between these two groups in high-grade gliomas. Only Ki67 > 0.1 was differentially expressed between lower- and high-grade gliomas in ATGs (P = 0.014). The high occurrence of H3 K27M mutation and Ki67 > 0.1, rare occurrence of IDH1 mutation, and MGMT promoter methylation in ATGs suggested that ATGs may be a distinct type of glioma entity.

6.
Signal Transduct Target Ther ; 6(1): 58, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568628

RESUMO

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.


Assuntos
/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Cordão Umbilical , Idoso , Aloenxertos , /fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Chem Commun (Camb) ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438691

RESUMO

A series of heterogeneous molecular catalysts by immobilizing nickel(ii) phthalocyanine (NiPc) onto different carbon supports were constructed to study the influence of the catalyst's microstructure on the performance of electrochemical carbon dioxide reduction reaction (CO2RR). The microporous structure of the electrocatalysts could influence CO2 transfer and therefore change the CO2 concentration at the surface of the catalyst, which singnificantly impacted the CO2RR performance.

8.
Org Biomol Chem ; 19(2): 467-475, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347527

RESUMO

Newly designed 3-((2,2,2-trifluoroethyl)amino)indolin-2-ones were used for the facile synthesis of chiral fluoroalkyl-containing 3,2'-spirooxindole γ-lactam products. The secondary amine-catalysed Michael/hemiaminalization cascade reaction of 3-((2,2,2-trifluoroethyl)amino)indolin-2-one with α,ß-unsaturated aldehydes followed by oxidation can easily produce the desired products in high yields (up to 86%) with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >95 : 5 dr).

9.
J Med Chem ; 63(24): 15752-15772, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33307675

RESUMO

ADP-mediated platelet aggregation is signaled through G protein-coupled receptors P2Y1 and P2Y12 on the platelet. The clinical effectiveness of inhibiting P2Y12 has been well established, and preclinical studies indicated that the inhibition of P2Y1 could provide equivalent antithrombotic efficacy as P2Y12 antagonists and reduce bleeding risks. On the basis of the 2-phenyl-1H-imidazole scaffold of our previously reported xanthine oxidase inhibitor WSJ-557, we first achieved the transition from the xanthine oxidase inhibitors to dual-target antagonists against P2Y1 and P2Y12. We described the structure-activity relationships of the 2-phenyl-1H-imidazole compounds, which led to the identification of the most potent antiplatelet agents, 24w and 25w, both showing a rapid onset of action in pharmacokinetic study. Furthermore, the rat model suggested that 24w demonstrated a wider therapeutic window than ticagrelor, displaying equivalent and dose-dependent antithrombotic efficacy with lower blood loss compared to ticagrelor at same oral dose. These results supported that 24w and 25w could be promising drug candidates.


Assuntos
Inibidores Enzimáticos/química , Inibidores da Agregação de Plaquetas/química , Antagonistas do Receptor Purinérgico P2Y/química , Receptores Purinérgicos P2Y12/química , Receptores Purinérgicos P2Y1/química , Xantina Oxidase/antagonistas & inibidores , Animais , Sítios de Ligação , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Estabilidade de Medicamentos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Meia-Vida , Humanos , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/metabolismo , Inibidores da Agregação de Plaquetas/farmacologia , Antagonistas do Receptor Purinérgico P2Y/metabolismo , Ratos , Receptores Purinérgicos P2Y1/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Relação Estrutura-Atividade , Ticagrelor/farmacologia , Xantina Oxidase/metabolismo
10.
Gigascience ; 9(12)2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347571

RESUMO

BACKGROUND: Sequencing technologies have advanced to the point where it is possible to generate high-accuracy, haplotype-resolved, chromosome-scale assemblies. Several long-read sequencing technologies are available, and a growing number of algorithms have been developed to assemble the reads generated by those technologies. When starting a new genome project, it is therefore challenging to select the most cost-effective sequencing technology, as well as the most appropriate software for assembly and polishing. It is thus important to benchmark different approaches applied to the same sample. RESULTS: Here, we report a comparison of 3 long-read sequencing technologies applied to the de novo assembly of a plant genome, Macadamia jansenii. We have generated sequencing data using Pacific Biosciences (Sequel I), Oxford Nanopore Technologies (PromethION), and BGI (single-tube Long Fragment Read) technologies for the same sample. Several assemblers were benchmarked in the assembly of Pacific Biosciences and Nanopore reads. Results obtained from combining long-read technologies or short-read and long-read technologies are also presented. The assemblies were compared for contiguity, base accuracy, and completeness, as well as sequencing costs and DNA material requirements. CONCLUSIONS: The 3 long-read technologies produced highly contiguous and complete genome assemblies of M. jansenii. At the time of sequencing, the cost associated with each method was significantly different, but continuous improvements in technologies have resulted in greater accuracy, increased throughput, and reduced costs. We propose updating this comparison regularly with reports on significant iterations of the sequencing technologies.

11.
World Neurosurg ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186787

RESUMO

OBJECTIVE: Given the rarity of patients with pineal glioblastoma (GBM), clinical characteristics, treatment, and prognostic factors are not well characterized. This study aimed to investigate these characteristics and identify the prognostic factors of overall survival (OS). METHODS: A retrospective analysis of newly diagnosed patients with pineal GBM, including our 3 cases and an additional 44 cases from published articles, was conducted. Survival analysis was performed by Kaplan-Meier analysis and Cox regression analysis was used to determine the prognostic factors. RESULTS: A total of 47 patients (28 males and 19 females) were enrolled, with a median age of 46 years (range, 5-74 years). Forty-four patients (90.9%) had preoperative obstructive hydrocephalus. Among 38 patients, 21 (55.3%) had distal leptomeningeal dissemination. Forty-five patients (95.7%) had resection/biopsy, 6 of whom had gross total resection, 22 had subtotal resection, 7 had partial resection, and 10 had biopsy. Adjuvant therapy included radiotherapy in 36 patients and chemotherapy in 27 patients. The median OS was 10.0 months. The 6-month, 1-year, and 2-year survival was 68.0%, 42.6%, and 17.0%, respectively. Cox regression analysis showed that patients receiving biopsy (P = 0.042) or chemotherapy (P = 0.029) had the better OS and these were regarded as independent prognostic factors. Further survival analysis showed that chemoradiotherapy had better survival benefit than other regimens. CONCLUSIONS: In this study, we summarized the characteristics of patients with pineal GBM and showed the correlation between clinical characteristics and prognosis. This study may give readers a deep understanding of these rare GBMs and provide some references for future management.

13.
Cancer Lett ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33166616

RESUMO

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.

14.
BMC Gastroenterol ; 20(1): 391, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213378

RESUMO

BACKGROUND: To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. METHODS: In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. RESULTS: The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). CONCLUSIONS: Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. TRIAL REGISTRATION: NCT01349348. Retrospectively registered May 2011.

15.
Sensors (Basel) ; 20(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003525

RESUMO

A light pen coordinate measuring system (LPCMS) is a kind of vision-based portable coordinate measuring technique. It implements coordinate measurement by analyzing the image of a light pen, which has several control points and a probe. The relative positions of control points need to be determined before measurement and serve as the measuring basis in LPCMS. How to accurately calibrate the relative positions of control points is the most important issue in system calibration. In this paper, a new method of control point position calibration based on a traditional coordinate measuring machine (CMM) is proposed. A light pen is fastened to the measuring arm of a CMM and performs accurate translational movement driven by the CMM. A camera is used to capture the images of control points at different positions, and the corresponding readings of the CMM are recorded at the same time. By establishing a separate coordinate system for each control point, the relative positions of the control points can be transformed to the differences of a series of translation vectors. Experiments show that the calibration repeatability of control point positions can reach 10 µm and the standard deviation of measurement of the whole LPCMS can reach 30 µm. A CMM is used to generate accurate translation, which provides a high accuracy basis of calibration. Through certain mathematical treatment, tremendous data acquired by moving the light pen to tens of thousands of different positions can be processed in a simple way, which can reduce the influence of random error. Therefore, the proposed method provides a high-accuracy solution of control point position calibration for LPCMS.

16.
Liver Int ; 40(11): 2685-2693, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33047868

RESUMO

BACKGROUND & AIM: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection. METHODS: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). RESULTS: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention. CONCLUSIONS: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis. LAY SUMMARY: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.

17.
Ann Transl Med ; 8(14): 890, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32793734

RESUMO

A solitary fibrous tumor (SFT) is a rare spindle cell tumor-derived from mesenchymal cells. It may be linked to the fusion of the NAB2-STAT6 gene caused by 12q chromosome rearrangement. It can occur in the connective tissue of any part of the body; however, it is most common in the pleura. Solitary fibrous tumors of the pleura (SFTP) are a persistent painless mass with slow growth. With the increase of the tumor, there will be corresponding compression symptoms. Pleural effusion is rare, and the cytology of pleural effusion is mostly negative. Occasionally, SFTP can induce paraneoplastic syndrome, distant metastasis, and malignant transformation. Lung function may have mild to moderate restrictive ventilation dysfunction. CT is a crucial method for the clinical diagnosis of SFTP. The histopathological features of SFTP are the coexistence of sparse and dense areas. CD34, CD99, Bcl-2, and vimentin are the most valuable immunohistochemical markers.The positive expression rate of STAT6 in benign SFT was even 100%. Adhesion or unclear boundary with surrounding tissues, pleural effusion or calcification, tumors with a maximum diameter greater than 10 cm, invasive growth, uneven density, metastasis or recurrence, paraneoplastic syndrome, moderate to severe cell heterogeneity, high Ki67 proliferation index, and low STAT6 expression suggest SFTP may be a malignant tumor. Gene analysis on next generation sequencing may help reveal the mutation characteristics of SFTP. Complete tumor resection is the gold standard of SFTP. Resectability is the most important prognostic factor. Age, size, mitosis, and necrosis are considered risk stratification factors for prognosis. Fortunately, 80% of SFTP are benign and have anexcellentprognosis but need long-term follow-up.We report a case of rapidly growing tumor with pleural effusion within 9 months, who was surgically treated and is currently under follow-up. And the literature is reviewed.

18.
Biomed Res Int ; 2020: 8379134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695822

RESUMO

External ventricular drainage (EVD) is widely used in patients with a traumatic brain injury (TBI). However, the EVD weaning trial protocol varies and insufficient studies focus on the intracranial pressure (ICP) during the weaning trial. We aimed to establish the relationship between ICP during an EVD weaning trial and the outcomes of TBI. We enrolled 37 patients with a TBI with an EVD from July 2018 to September 2019. Among them, 26 were allocated to the favorable outcome group and 11 to the unfavorable outcome group (death, post-traumatic hydrocephalus, persistent vegetative state, and severe disability). Groups were well matched for sex, pupil reactivity, admission Glasgow Coma Scale score, Marshall computed tomography score, modified Fisher score, intraventricular hemorrhage, EVD days, cerebrospinal fluid output before the weaning trial, and the complications. Before and during the weaning trial, we recorded the ICP at 1-hour intervals to calculate the mean ICP, delta ICP, and ICP burden, which was defined as the area under the ICP curve. There were significant between-group differences in the age, surgery types, and intensive care unit days (p = 0.045, p = 0.028, and p = 0.004, respectively). During the weaning trial, 28 (75.7%) patients had an increased ICP. Although there was no significant difference in the mean ICP before and during the weaning trial, the delta ICP was higher in the unfavorable outcome group (p = 0.001). Moreover, patients who experienced death and hydrocephalus had a higher ICP burden, which was above 20 mmHg (p = 0.016). Receiver operating characteristic analyses demonstrated the predictive ability of these variables (area under the curve [AUC] = 0.818 [p = 0.002] for delta ICP and AUC = 0.758 [p = 0.038] for ICP burden > 20 mmHg). ICP elevation is common during EVD weaning trials in patients with TBI. ICP-related parameters, including delta ICP and ICP burden, are significant outcome predictors. There is a need for larger prospective studies to further explore the relationship between ICP during EVD weaning trials and TBI outcomes.

19.
Lancet Neurol ; 19(8): 670-677, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702336

RESUMO

BACKGROUND: Large-scale studies are required to better characterise traumatic brain injury (TBI) and to identify the most effective treatment approaches for TBI. However, evidence is scarce and mostly originates from high-income countries. We aimed to describe the existing care for patients with TBI and the outcomes in China. METHODS: The Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry is a prospective, multicentre, longitudinal, observational study done in 56 neurosurgical centres across China. We collected data of patients who were admitted to hospital with a clinical diagnosis of TBI and an indication for CT. Patients who were discharged directly from the emergency room were excluded. The primary endpoint was survival on discharge. Prognostic analyses were applied to identify predictors of mortality. Variations in mortality were compared between centres and provinces within China. Mortality was compared with expected mortality, estimated using the CRASH basic model. This study was registered with ClinicalTrials.gov, NCT02210221. FINDINGS: From Dec 22, 2014, to Aug 1, 2017, 13 627 patients with TBI from 56 centres were enrolled in the registry. Data from 13 138 patients from 52 hospitals in 22 provinces of China were analysed. Most patients were male (9782 [74%]), with a median age of 48 years (IQR 33-61). The median Glasgow Coma Scale (GCS) score was 13 (IQR 9-15), and the leading cause of injury was road-traffic incident (6548 [50%]). Overall, 637 (5%) patients died, including 552 (20%) patients with severe TBI. Age, GCS score, injury severity score, pupillary light reflex, CT findings (compressed basal cistern and midline shift ≥5 mm), presence of hypoxia, systemic hypotension, altitude higher than >500 m, and GDP per capita were significantly associated with survival in all patients with TBI. Variation in mortality existed between centres and regions. The expected 14-day mortality was 1116 (13%), but 544 (7%) deaths within 14 days were observed (observed to expected ratio 0·49 [95% CI 0·45-0·53]). INTERPRETATION: The results show differences in mortality between centres and regions across China, which indicates potential for identifying best practices through comparative effectiveness research. The risk factors identified in prognostic analyses might contribute to developing benchmarks for assessing quality of care. FUNDING: None.


Assuntos
Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/terapia , Adolescente , Adulto , Idoso , Lesões Encefálicas Traumáticas/diagnóstico , China , Feminino , Escala de Coma de Glasgow , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
J Dig Dis ; 21(9): 519-525, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700794

RESUMO

OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.

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