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1.
Med Ultrason ; 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32905570

RESUMO

The evaluation of lymph nodes (LN) using ultrasound requires a high level of clinical and sonographic competence. This "pictorial essay" is intended to illustrate eye-catching examples of relevant "clinical-sonographic visual diagnoses" of LNs. We provide typical images and take home messages of eye-catching features to illustrate the featured publications.The first part included the introduction into the subject, indications for US examination and the widely accepted recognized features for LN characterization. The key features for the differential diagnosis of suspected lymphadenopathy and benign lymphadenopathy are illustrated. In the second part eye-catching features of malignant lymphadenopathy and the differential diagnosis of carcinoma and lymphoma are shown.

2.
Eur J Med Chem ; 207: 112723, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32920426

RESUMO

Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.

3.
J Am Heart Assoc ; 9(18): e017147, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32912018

RESUMO

Background Octogenarians (≥80 years old) are high-risk patients for acute aortic dissection (AAD) surgery. However, no population-based study has investigated the late outcomes of AAD surgery in octogenarians. This study aimed to investigate the late outcomes of AAD surgery in octogenarians. Methods and Results A total of 3998 patients who received AAD surgery from 2005 to 2013 were identified from the Taiwan National Health Insurance Research Database. In-hospital complications and late outcomes including all-cause mortality, major adverse cardiac and cerebrovascular event, respiratory failure, and redo aortic surgery were evaluated. The risks of late outcomes between octogenarians and nonoctogenarians were compared using the multivariable Cox proportional hazard model or Fine and Gray competing model. The numbers of the octogenarians who underwent type A and B AAD surgeries were 206 (6%; 206/3423) and 79 (13.7%; 79/575), respectively. Compared with the nonoctogenarians, the type A octogenarians had higher risks of in-hospital mortality and several in-hospital complications, whereas the type B octogenarians did not. Furthermore, compared with the nonoctogenarians, the type A octogenarians had a higher risk of all-cause mortality (61.7% vs 32.5%; hazard ratio [HR], 2.35; 95% CI, 1.95-2.84) and a higher cumulative incidence of major adverse cardiac and cerebrovascular event and respiratory failure, and the type B octogenarians demonstrated a higher risk of all-cause mortality (44.3% vs 30.4%; HR, 1.74; 95% CI, 1.18-2.55). The octogenarians receiving AAD surgeries had higher mortality rates than the normal octogenarian population. Conclusions Octogenarians receiving AAD surgeries exhibit worse late outcomes than nonoctogenarian counterparts.

4.
J Photochem Photobiol B ; 211: 112015, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32927294

RESUMO

Photodynamic therapy (PDT) is a non-invasive and innovative therapeutic approach which has been increasingly applied in clinical cancer therapy. As the central element of PDT, the development of novel photosensitizers (PSs) with longer absorption wavelength, proper lipophilic/hydrophilic profiles, target tissue selectivity, and higher photo-/lowest dark-cytotoxicity is a challenging task. Previously, we designed and synthesized a series of novel long-wavelength chlorin e6 (Ce6)-based PSs via introducing aromatic groups to the vinyl of Ce6 skeleton. The new formed compounds with π-extension system exhibited improved photodynamic effects and spectral characteristics. Among these π-conjugated chlorin PSs, (E)-32-(4-methoxyphenyl)-chlorin e6, named A15, was expected to be a potent antitumor candidate as a PDT agent due to its good photobiological properties. Herein, in this work, we evaluated the effectiveness of A15 in cancer PDT. In vitro, a novel rare earth probe, ATTA-Eu3+ was applied to detect the singlet oxygen (1O2) production of A15 in solution and human hepatoma HepG2 cells, respectively. Moreover, A15 exhibited strong phototoxicity and weak dark cytotoxity to HepG2 cells. In H22 tumor bearing mice, A15 showed excellent tumor accumulation ability via i.v. administration and induced tumor regression, followed by laser treatment. These results indicated that A15 is a potential novel π-extension chlorin-type PS for PDT applications.

5.
Med Ultrason ; 22(3): 2634, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32898206

RESUMO

The evaluation of lymph nodes (LNs) using ultrasound requires a high level of clinical and sonographic competence. This "pictorial essay" is intended to illustrate eye-catching examples of relevant "clinical-sonographic visual diagnoses" of LNs. We provide typical images and take-home messages of eye-catching features to illustrate the featured publications.The first part includes "important differential diagnoses of eye-catching features of suspected lymphadenopathy" and "benign lymphadenopathy". The second part will include "Eye-catching features of malignant lymphadenopathy, both carcinoma and lymphoma".

6.
Endosc Ultrasound ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32883923

RESUMO

Recently, we introduced a series of papers describing on how to perform certain techniques and controversies in EUS. In the first paper, "What should be known before performing EUS examinations, Part I," the authors discussed clinical information and whether other imaging modalities should be needed before embarking in EUS examination. In Part II, some technical controversies on how EUS is performed are discussed from different points of view by providing the relevant available evidence. Herewith, we describe on how to perform EUS-guided fine needle tattooing (FNT) in daily practice. The aim of this paper is to discuss pros and cons for several issues including historical remarks, injecting material, technical approach, and how to perform EUS-FNT including argues in favor and against.

7.
Rheumatol Ther ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32876903

RESUMO

INTRODUCTION: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment. METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics. RESULTS: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups. CONCLUSIONS: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period. TRIAL REGISTRATION: NCT02265705.

8.
Sci Adv ; 6(32): eabc7288, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32821848

RESUMO

Proteostasis declines with age, characterized by the accumulation of unfolded or damaged proteins. Recent studies suggest that proteins constituting pathological inclusions in neurodegenerative diseases also enter and accumulate in mitochondria. How unfolded proteins are managed within mitochondria remains unclear. Here, we found that excessive unfolded proteins in the mitochondrial matrix of yeast cells are consolidated into solid-phase inclusions, which we term deposits of unfolded mitochondrial proteins (DUMP). Formation of DUMP occurs in mitochondria near endoplasmic reticulum-mitochondria contact sites and is regulated by mitochondrial proteins controlling the production of cytidine 5'-diphosphate-diacylglycerol. DUMP formation is age dependent but accelerated by exogenous unfolded proteins. Many enzymes of the tricarboxylic acid cycle were enriched in DUMP. During yeast cell division, DUMP formation is necessary for asymmetric inheritance of damaged mitochondrial proteins between mother and daughter cells. We provide evidence that DUMP-like structures may be induced by excessive unfolded proteins in human cells.

9.
Parkinsonism Relat Disord ; 78: 116-121, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32814229

RESUMO

INTRODUCTION: Due to diverse symptoms of spinocerebellar ataxia type 3 (SCA3) and the high prevalence of SCA3 in China, a more in-depth study of Chinese SCA3 patients in a large cohort is well merited. METHODS: During the last 10 years, 730 patients and 133 premanifest individuals from 667 SCA3 families genetically confirmed to have SCA3 were enrolled from three leading academic hospitals in China. The clinical profile and genotype-phenotype correlation were analyzed. RESULTS: A quadratic equation best explained the relationship between the logarithmically transformed age at onset (AAO) and expanded CAG repeats (expCAGs) (r2 = 0.634, p < 0.001). The expCAG and AAO in Asian populations and western populations were compared with the Chinese population. SCA3 individuals had shorter normal CAG repeats (norCAGs) than healthy controls (Mann-Whitney, p < 0.0001). Most (92.1%) SCA3 patients had gait-ataxia onset. Their AAO and expCAGs were not significantly different from SCA3 patients with non-gait-ataxia onset. Limb ataxia and pyramidal impairment occurred less in patients with disease duration >10 years. Intriguingly, onset after parturition happened in 10 female patients with the AAO of 26.7 ± 4.3 years and the expCAG of 77.4 ± 1.4 repeats. Five out of 12 patients with subtype V and larger expCAGs (78.8 ± 4.8 repeats) suffered from spastic gait initially, and 10 out of 12 showed no limb ataxia. Nystagmus happened most frequently (10.5%) in premanifest individuals. CONCLUSION: We demonstrated the genotype-phenotype correlation in the largest cohort of SCA3 individuals to date, and interestingly found some new phenomena in Chinese SCA3 individuals.

10.
J Viral Hepat ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810891

RESUMO

To date, studies that focus on treatment of e antigen-negative chronic hepatitis B virus-infected children with advanced fibrosis are extremely limited. This puts these patients at risk of rapid disease progression. Our study aimed to investigate the efficacy of combination antiviral therapy in this population. We prospectively enrolled treatment-naïve paediatric patients between 1 year and 12 years of age who had e antigen-negative chronic hepatitis B and histologically proven advanced fibrosis. All patients received de novo combination therapy with lamivudine (LAM) and interferon-α (IFN) for 12 months and then were clinically followed up. The main outcome measure was rate of serum hepatitis B surface antigen (HBsAg) loss at month 12 of treatment. A total of 14 paediatric patients were enrolled, including 9 boys and 5 girls. All patients achieved undetectable HBV DNA levels at month 9 of treatment. A total of 5 patients (35.7%) achieved HBsAg loss at month 12 and finally developed HBsAg seroconversion. Four patients who did not clear HBsAg underwent second liver biopsy, and histological evaluation revealed significant improvements in all of them. As a serum fibrosis marker, aspartate aminotransferase-to-platelet ratio index after 12-month treatment in the 14 patients showed a significant improvement compared with that at baseline (P = .0021). No serious adverse events were observed during the study. Combination antiviral therapy is beneficial to e antigen-negative chronic hepatitis B virus-infected paediatric patients with advanced fibrosis. Further studies with larger cohorts are required.

11.
Endocrine ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852733

RESUMO

PURPOSE: To establish a practical and simplified Chinese thyroid imaging reporting and data system (C-TIRADS) based on the Chinese patient database. METHODS: A total of 2141 thyroid nodules that were neither cystic nor spongy were used in the current study. These specimens were derived from 2141 patients in 131 alliance hospitals of the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The ultrasound features, including location, orientation, margin, halo, composition, echogenicity, echotexture, echogenic foci and posterior features were assessed. Univariate and multivariate analyses were performed to investigate the association between ultrasound features and malignancy. The regression equation, the weighting, and the counting methods were used to determine the malignant risk of the thyroid nodules. The areas under the receiver operating characteristic curve (Az values) were calculated. RESULTS: Of the 2141 thyroid nodules, 1572 were benign, 565 were malignant, and 4 were borderline. Vertical orientation, ill-defined, or irregular margin (including extrathyroidal extension), microcalcifications, solid, and markedly hypoechoic were positively associated with malignancy, while comet-tail artifacts were negatively associated with malignancy. The logistic regression equation yielded the highest Az value of 0.913, which was significantly higher than that obtained using the weighting method (0.893) and the counting method (0.890); however, no significant difference was found between the latter two. The C-TIRADS, based on the counting method, was designed following the principle of balancing the diagnostic performance and sensitivity of the risk stratification with the ease of use. CONCLUSIONS: A relatively simple C-TIRADS was established using the counting value of positive and negative ultrasound features.

13.
J Interv Cardiol ; 2020: 9506124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774190

RESUMO

Background: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain. Methods: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years. Results: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001). Conclusions: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD.

14.
Med Sci Monit ; 26: e923621, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32680979

RESUMO

BACKGROUND The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit ß5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. MATERIAL AND METHODS JHU-011 and FaDu cells were used as effector cells in this study. By means of 6°Co γ-irradiation, the construction of stable cell lines of the silenced proto-oncogene c-Abl, and the addition of exogenous tyrosine kinase inhibitor (TKI) and activator, the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms in both cell lines were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western blot. RESULTS Ionizing radiation upregulated the transcription level of the alternatively spliced isoform of PSMB8, E2, in both cell lines, thereby upregulating the mRNA and protein levels of PSMB8. The silencing of the proto-oncogene c-Abl and the activation and inhibition of its kinetic kinase product can affect the transcription and protein levels of PSMB8. CONCLUSIONS Ionizing radiation can significantly upregulate the mRNA and protein levels of PSMB8, which happens through the upregulation of its splicing isoform E2. The proto-oncogene c-Abl and its kinetic kinase protein product can regulate the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms.

15.
Insect Sci ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686293

RESUMO

Conopomorpha sinensis is the dominant borer pest of Litchi chinensis (litchi) and Euphoria longan (longan) in China. Control of C. sinensis is difficult because of its cryptic life habit; thus, an effective ovicide could be beneficial. The larvicidal effects of diflubenzuron (DFB) have been documented in many insect pest species. Therefore, DFB might be a useful ovicide to control C. sinensis. However, the detailed mode of action of DFB interference with insect molting and egg hatching is unclear. Thus, we studied alterations in expression of all genes potentially affected by DFB treatment using a transcriptome approach in 2-d-old C. sinensis eggs. Clean reads were assembled to generate 203 455 unigenes and 440 558 transcripts. A total of 4625 differently expressed genes, which included 2670 up-regulated and 1955 down-regulated unigenes, were identified. Chitin binding and chitin metabolic processes were among the most significant enriched pathways according to Gene Ontology analyses. Most of the genes that encode enzymes involved in the chitin biosynthesis pathway were unaffected, whereas genes that presumably encode cuticle proteins were up-regulated. Furthermore, altered expression patterns of 10 genes involved in the chitin biosynthesis pathway of C. sinensis embryos were observed in response to DFB treatment at different time points by quantitative reverse transcription polymerase chain reaction. We also observed abnormal development; there was reduced chitin content and modulated chitin distribution of newly hatched larvae, and altered egg hatching. Our findings illustrate an ovicidal effect of DFB on C. sinensis, and reveal more molecular consequences of DFB treatment on insects.

16.
Ultrasound Med Biol ; 46(10): 2579-2604, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713788

RESUMO

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications. The 2012 guideline requires updating as, previously, the differences in the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients.

17.
Mol Genet Genomic Med ; 8(9): e1314, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32643267

RESUMO

BACKGROUND: Homozygous spinocerebellar ataxia type 3 (SCA3) patients, which have an expanded cytosine-adenine-guanine (CAG) repeat mutation in both alleles of ATXN3, are extremely rare. Clinical features and genetic characteristics of them were seldom studied. METHODS: We analyzed seven newly homozygous SCA3 patients from five families and 14 homozygotes reported previously. An additional cohort of 30 heterozygous SCA3 patients were analyzed to compare age at onset (AAO). RESULTS: Two out of seven SCA3 homozygotes had the minimum CAG repeats reported so far (55/56 and 56/58). Five patients appeared peripheral neuropathy and two had mild cognitive impairment. The AAO was significantly inversely correlated with both the large and small expanded CAG repeats (r = -.7682, p < .0001). The AAO was significantly earlier in homozygous SCA3 than heterozygous ones (32.81 ± 11.86 versus. 49.90 ± 9.73, p < .0001). In addition, the AAO of our seven homozygotes is elder compared to those reported previously (41.29 years vs. 28.57 years), which may be related to the fewer CAG repeats in our seven patients. CONCLUSION: Gene dosage effect may play an important role in the AAO and severity of disease, and homozygosity for ATXN3 enhances phenotypic severity. Our findings expand clinical features and genetic characteristics of homozygous SCA3 patients.

18.
Huan Jing Ke Xue ; 41(6): 2936-2941, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608811

RESUMO

Coal gangue is a harmful solid waste product of coal mining. When it accumulates for a long time, it becomes harmful to the surroundings. To investigate the adverse effect of coal gangue on the surrounding environment, this study investigated the effects of coal gangue and its downstream village on the growth toxicity and genotoxicity of barley at different dilution concentrations (1:27, 1:9, 1:3, and 1:1) via hydroponic experiments. As a result, low concentration coal gangue showed a slight promotion effect on the growth of roots and shoots of barley, while coal gangue and village soil, which have a high concentration, could seriously inhibit their germination and growth. At the same time, with the increase of the concentration of coal gangue, malondialdehyde (MDA) in barley leaves increased, and chlorophyll (Chl) increased first and then decreased, while the village soil showed a lower toxic effect. In addition, our results showed that higher concentrations of coal gangue and village soil could decrease the mitotic index and increase the micronucleus rate in root tip cells, indicating that the toxicity mechanism of coal gangue to barley may be involved in genotoxicity. These results provide experimental evidence for the ecological risk assessment of the coal gangue and its surrounding environment.

19.
Mol Genet Genomic Med ; : e1438, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32729243

RESUMO

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder with high clinical heterogeneity. Twin study is valuable to estimate the contributions of gene and/or environment to phenotypic variance. However, SCA3 twins were extremely sparse and rarely reported. METHODS: A pair of monozygotic twins with SCA3 was assessed using well-acknowledged scales. Genetic modifiers and methylation levels were determined by Sanger sequencing and pyrosequencing. RESULTS: Sharing identical CAG repeat lengths, the twins presented with similar symptoms, whereas, the younger sister had an earlier age at onset of two years. The occurrence time and severity of constipation, blepharospasm and fasciculation were markedly different between the twins. Notable methylation level differences of several CpG sites existed between the twins. CONCLUSIONS: It is the first time to report SCA3 monozygotic twin worldwide. The role of epigenetic factors in the phenotype variance deserved more attention. The DNA methylation may influence the phenotypic variance by altering the occurrence time and severity of symptoms, indicating its potential in alleviating the disease.

20.
Stroke Vasc Neurol ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611728

RESUMO

BACKGROUND: The risk of symptomatic intracranial haemorrhage (sICH) after thrombolysis is low but severe. Lower dose of alteplase may reduce the risk of sICH. We aim to identify subsets of patients who could benefit from lower dose of alteplase compared with standard dose. METHODS: Data from two observational registries were pooled together. A total of 3479 patients who had acute ischaemic stroke were entered into the interaction tree model. The response variable was the rate of sICH per the definition of the National Institute of Neurological Disorders and Stroke Study. Clinical improvement was measured by the National Institutes of Health Stroke Scale (NIHSS) and defined as NIHSS 0 or 1 or an improvement of more than 4 points (within 7 days or at discharge). Rare event logistic regression was performed to analyse the OR of safety outcome. RESULTS: To optimise the interaction effect between tissue plasminogen activator (tPA) dosage (standard/lower) and patient subgroups, three subgroups based on the severity of stroke were identified: (1) NIHSS ≤4, (2) NIHSS between 5 and 14, and (3) NIHSS ≥15. The estimated difference of OR of having sICH was 2.71 (95% CI 0.80 to 7.69, p=0.10) for mild, 0.13 (95% CI 0.02 to 0.68, p=0.01) for moderate, and 0.65 (95% CI 0.19 to 2.55, p=0.52) for severe, respectively. In addition, patients who had moderate stroke treated with lower dose had comparable efficacy outcome (OR 1.23, 95% CI 0.71 to 2.13, p=0.45). CONCLUSION: Our analysis demonstrated that in patients who had moderate stroke, lower doses of alteplase are associated with significant sICH reduction and non-inferior performance in efficacy, compared with those in the standard dose group. TRIAL REGISTRATION NUMBER: The TIMS-China was a national prospective stroke registry on thrombolytic therapy using intravenous tPA in patients who had acute ischaemic stroke. The results were initially published in 2012 without a clinical trial registration number. The Shanghai Stroke Service System was registered at www.clinicaltrial.gov (NCT02735226).

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