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1.
J Cell Mol Med ; 28(14): e18546, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39046458

RESUMO

Heart failure (HF) prognosis depends on various regulatory factors; microRNA-128 (miR-128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/ß-catenin pathway, is supposed to be regulated by miR-128. This study investigates the interaction between miR-128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR-128's effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR-128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR-128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR-128 and MDFI sequences. miR-128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR-128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR-128 levels upregulated Wnt1 and ß-catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR-128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR-128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/ß-catenin pathway. Suppression of miR-128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR-128/MDFI interplay in HF treatment.


Assuntos
Apoptose , Cardiomegalia , Proliferação de Células , Insuficiência Cardíaca , MicroRNAs , Miócitos Cardíacos , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Apoptose/genética , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Proliferação de Células/genética , Camundongos , Masculino , Humanos , Via de Sinalização Wnt/genética , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , beta Catenina/metabolismo , beta Catenina/genética , Proteína Wnt1/metabolismo , Proteína Wnt1/genética
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1006517

RESUMO

@#Objective     To investigate the relationship between preoperative mean daily step counts and pulmonary complications after thoracoscopic lobectomy in elderly patients. Methods     From 2018 to 2021, the elderly patients with pulmonary complications after thoracoscopic lobectomy were included. A 1∶1 propensity score matching was performed with patients without pulmonary complications. The clinical data were compared between the two groups. Results    Totally, 100 elderly patients with pulmonary complications were enrolled, including 78 males and 22 females, aged 66.4±4.5 years. And 100 patients without pulmonary complications were matched, including 71 males and 29 females aged 66.2±5.0 years. There was no significant difference in the preoperative data between the two groups (P>0.05). Compared to the patients with pulmonary complications, the ICU stay was shorter (8.1±4.4 h vs. 12.9±7.5 h, P<0.001), the first out-of-bed activity time was earlier (8.8±4.5 h vs. 11.2±6.1 h, P=0.002), and the tube incubation time was shorter (19.3±9.2 h vs. 22.5±9.4 h, P=0.015) in the patients wihout pulmonary complications. There was no statistical difference in other perioperative data between the two groups (P>0.05). The mean daily step counts in the pulmonary complications group were significantly less than that in the non-pulmonary complications group (4 745.5±2 190.9 steps vs. 6 821.1± 2 542.0 steps, P<0.001). The daily step counts showed an upward trend for three consecutive days in the two groups, but the difference was not significant. Conclusion     The decline of preoperative mean daily step counts is related to pulmonary complications after thoracoscopic lobectomy in elderly patients. Recording daily step counts can promote preoperative active exercise training for hospitalized patients.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012415

RESUMO

Two review articles summarizing the fifth edition of the World Health Organization (WHO) classification of haematolymphoid tumours were officially published on Leukemia journal in 2022. This article briefly summarizes some important advances and changes in the fifth edition of WHO classification of haematolymphoid tumours, and describes how to apply the classification dialectically and reasonably in the daily practice of pathologists, so as to accurately guide clinical treatments.


Assuntos
Humanos , Neoplasias , Organização Mundial da Saúde
4.
Chinese Journal of Pathology ; (12): 6-11, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012416

RESUMO

The 5th edition WHO classification of B-cell tumors is a systematic update to the fourth revised version of the classification. The changes include updated names of entities, sharpened diagnostic criteria, and upgrades from provisional to definite entities. This review focuses on the changes in the content of each chapter of B-cell tumors, facilitating domestic colleagues engaged in the diagnosis and treatment of lymphohematopoietic tumors to understand the latest progress and guide daily work.


Assuntos
Humanos , Organização Mundial da Saúde , Linfoma de Células B/diagnóstico
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1021648

RESUMO

BACKGROUND:Studies demonstrated that miR-135a-5p was highly expressed in mouse embryonic palatal mesenchymal cells with cleft palate induced by dexamethasone.The primary cilium and its mediated Shh signaling pathway were involved in the autophagy of mouse embryonic palatal mesenchymal cells.It is speculated that miR-135a-5p may regulate autophagy in mouse embryonic palatal mesenchymal cells through primary cilia and its mediated Shh signaling pathway. OBJECTIVE:To investigate the regulatory effect of miR-135a-5p on autophagy of mouse embryonic palatal mesenchymal cells. METHODS:In vitro,palatal mesenchymal cells from C57BL/6J mouse embryos were extracted and cultured.Cell transfections were set up as follows:(1)the cells were divided into control group,miR-135a-5p negative control group and miR-135a-5p mimic group;(2)NC+miR-NC group,KIF3B overexpression group,and miR-135a-5p+KIF3B group:qRT-PCR was performed to verify transfection efficiency of miR-135a-5p and KIF3B.A transmission electron microscope was used to observe the number of autophagosome/autophagolysosome in the cells of each group.The degree of fluorescence expression of autophagy marker LC3B was determined by the immunofluorescence technique.The protein expression of KIF3B,LC3 and P62 was determined by western blot assay.(3)The cells were divided into miR-135a-5p negative control group,and SAG treated group,and SAG+miR-135a-5p group.qRT-PCR was used to detect the mRNA expression levels of Gli3,a key transcription factor downstream of Shh signaling.The protein expressions of autophagy-related proteins LC3 and P62 were detected by western blot assay. RESULTS AND CONCLUSION:(1)After overexpression of miR-135a-5p,the number of autophagosome/autophagolysosome was significantly increased(P<0.01).The fluorescence density of LC3B increased significantly(P<0.01);the protein expression of KIF3B and P62 decreased(P<0.01),and the protein expression of LC3 increased.(2)After overexpression of KIF3B,the number of autophagosome/autophagolysosome was significantly decreased(P<0.01);the fluorescence density of LC3B was decreased(P<0.01);the protein expression of P62 was increased(P<0.01),and the protein expression of LC3 was decreased(P<0.01).Targeted expression of KIF3B was inhibited by miR-135a-5p(P<0.01);the number of autophagosome/autophagolysosome,the fluorescence intensity of LC3B as well as the protein expression of LC3 were reversed(P<0.01)and the protein expression of P62 was decreased(P<0.01).(3)SAG significantly increased the mRNA expression of Gli3(P<0.01),increased the protein expression of P62(P<0.01),and decreased the protein expression of LC3(P<0.01).When miR-135a-5p was added,Gli3 mRNA expression was significantly decreased(P<0.01);P62 protein expression was decreased(P<0.01),and LC3 protein expression was reversed(P<0.01).(4)These results indicate that miR-135a-5p targets the inhibition of KIF3B and promotes autophagy in mouse embryonic mesenchymal cells possibly by negatively regulating the Shh signaling pathway.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1030201

RESUMO

[Objective]To explore the influence of WANG Yangming's theory of mind in the Ming Dynasty on ZHANG Jingyue's thought of treating depression.[Methods]With the help of historical literature research methods of distinguishing academic chapters and examining the origin and development of mirror studies,this study aims to sort out ZHANG Jingyue's grand perspective based on the ontology,physical application,and cultivation of Yangming's theory of mind,establishes a new theory of traditional Chinese medicine for the treatment of depression,and elucidates the inheritance and development of ZHANG Jingyue's thought of treating depression on Yangming's theory of mind.[Results]The core issues of Yangming's theory of mind were the relationship between human mind and emotions,as well as the relationship between emotion and mood.ZHANG Jingyue established a theory of depression diagnosis and treatment that combined emotion and mood,illness due to depression,discussed depression from deficiency,and treated depression through knowledge and action,reflecting his medical thinking's inheritance and development of Yangming's theory of mind.[Conclusion]Based on the analysis of the origin and development of Yangming's theory of mind,it can be concluded that ZHANG Jingyue's thought of treating depression inherits and exerts the profound meaning of Yangming's theory of mind,develops and constructs a highly innovative theory for the diagnosis and treatment of depression in traditional Chinese medicine,and analyzes his thought of treating depression under the approach of Yangming's theory of mind,which is beneficial for the diagnosis and treatment of depression in traditional Chinese medicine.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1031606

RESUMO

【Objective】 To analyze the clinical features of patients with infected pancreatic necrosis (IPN) complicated with fungal infection so as to identify possible risk factors for death. 【Methods】 We analyzed the clinical data of patients with IPN admitted to Xuanwu Hospital Capital Medical University from January 1, 2017 to December 31, 2021. According to the results of pancreatic necrotic tissue and drainage fluid culture, the patients were divided into the group with fungal infection and the group without fungal infection. The baseline data, clinical features and outcomes of the two groups were compared, and the risk factors for death in patients with fungal infection were analyzed. 【Results】 We included a total of 214 patients in the study, of whom 49 patients in the fungal infection group had wider necrotic involvement, lower hematopoietic volume, and higher blood glucose at admission. Patients with fungal infection had a higher proportion of multidrug-resistant bacteria (MDRB), and hospital and ICU stay as well as parenteral nutrition duration were also longer. In the group of patients with fungal infection, the proportion of patients undergoing surgery did not increase (P>0.05), but the proportion of patients with perioperative organ failure and death was higher (P<0.05). Candida albicans (44.8%) was the most common fungus detected, followed by Candida parapsilosis (28.6%) and Candida tropicalis (8.2%). Logistic regression analysis showed that MDRB infection (OR=1.37, 95% CI:1.02-1.83), fungemia (OR=1.53, 95% CI:1.06-2.23), hyperglycemia (OR=1.65, 95% CI:1.28-2.10), new organ failure (OR=1.65, 95% CI:1.19-2.29) and bleeding complications (OR=1.64, 95% CI:1.28-2.10) after surgery were risk factors for death in patients with fungal infection. 【Conclusion】 Fungal infection increases mortality in patients with IPN and the incidence of new organ failure after surgery. Attention to fungemia, MDRB infection, hyperglycemia, organ failure and postoperative bleeding can help reduce the risk of death.

8.
Journal of Clinical Hepatology ; (12): 594-599, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013143

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world, and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma, so it is particularly important to curb the development and progression of NAFLD in a timely manner. However, due to its complex pathogeneses, there are currently no effective methods for radical treatment. As a new generation of probiotics, Akkermansia muciniphila (Akk bacteria) can improve metabolic disorders of the body, and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases, especially NAFLD. Therefore, this article briefly reviews the mechanism of action of Akk bacteria in NAFLD, in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1045653

RESUMO

@#Abstract: The new generation of artificial intelligence technology, represented by deep learning, has emerged as a crucial driving force in the advancement of new drug research and development. This article creatively proposes a workflow named “Molecular Factory” for the design and optimization of drug molecules based on artificial intelligence technology. This workflow integrates intelligent molecular generation models, high-performance molecular docking algorithms, and accurate protein-ligand binding affinity prediction methods. It has been integrated as a core module into DrugFlow, a one-stop drug design software platform, providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds. Utilizing the “Molecular Factory” module, we conducted the research of second-generation inhibitors against Menin that can combat drug resistance. Through the integration of computational and experimental approaches, we rapidly identified multiple promising compounds. Among them, compound RG-10 exhibited the IC50 values of 9.681 nmol/L, 233.2 nmol/L, and 40.09 nmol/L against the wild-type Menin, M327I mutant, and T349M mutant, respectively. Compared to the positive reference molecule SNDX-5613, which has entered Phase II clinical trials, RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants. These findings fully demonstrate the unique advantages of the "Molecular Factory" technology in practical drug design and development scenarios. It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures, holding significant value and profound implications for advancing new drug discovery.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1046010

RESUMO

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10th and decreased to 0.37 on March 15th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4th, 2022.


Assuntos
Feminino , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Epidemias , Instituições de Assistência Ambulatorial , COVID-19 , Fazendeiros , Febre
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1046333

RESUMO

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10th and decreased to 0.37 on March 15th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4th, 2022.


Assuntos
Feminino , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Epidemias , Instituições de Assistência Ambulatorial , COVID-19 , Fazendeiros , Febre
12.
Chinese Journal of Zoonoses ; (12): 90-94, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1024894

RESUMO

This study was aimed at performing epidemiologic investigation of the first psittacosis death case in Hangzhou City,to provide a reference for the investigation and disposal of psittacosis cases,as well as prevention and control.Epidemio-logic data were collected through field epidemiologic investigation,and close contacts and environmental samples were collected for pathogenicity testing.The first symptom in the patient was cough,which did not raise concerns at the time.Several days later,the patient developed abdominal distension and black stools,and visited two medical institutions for treatment and hospi-talization.The patient's sputum and peripheral blood were tested for Chlamydia psittaci infection by metagenomic analysis via next-generation sequencing.Samples collected from the patient's family members,close contacts,and home environment test-ed negative with real-time quantitative polymerase chain reaction.The patient later died of gastrointestinal bleeding.This article is the first report of a case of psittacosis contracted from exposure to a sick parrot in Hangzhou City,in a patient who died be-cause of an underlying disease.Operational training should be provided for medical personnel,and early diagnosis with mNGS and treatment of patients with underlying diseases should be performed as early as possible to avoid fatality.In addition,health education should be carried out to raise public awareness of the disease.

13.
Chinese Journal of Trauma ; (12): 97-106, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1027012

RESUMO

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

14.
Front Pharmacol ; 14: 1136960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441535

RESUMO

Introduction: Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma. Methods: The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model. Results: This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib. Discussion: To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.

16.
International Eye Science ; (12): 1250-1259, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978614

RESUMO

AIM: To investigate the role and mechanism of N6-methyladenosine(m6A)methyltransferase 3(METTL3)in the pathogenesis of diabetic cataract.METHODS: We cultured SRA01/04 cells in low and high sugar media for 24h and measured changes in epithelial-mesenchymal transition(EMT)indicators(E-Cadherin, N-Cadherin, ZO-1 and α-SMA)using RT-qPCR and Western blot assays. Cell migration was also assessed using transwell and scratch assays. To investigate the expression level and localization of METTL3 in human lens anterior capsules tissues. Additionally, we used m6A dot blot assay to detect the m6A methylation level of cells cultured in low and high glucose media for 24h, and employed RT-qPCR and Western blot experiments to detect RNA and protein expression of METTL3 in cells. We then treated the cells with METTL3 inhibitor and measured changes in EMT markers by RT-qPCR and Western blot; m6A methylation level was detected by m6A dot blot test; cell migration was detected by Transwell. Finally, the expression of transforming growth factor-β(TGFβ1)in cultured cells was assessed by immunofluorescence staining and the expression levels of TGFβ1 and SNAIL in cells were determined using RT-qPCR and Western blot.RESULTS: Under high glucose conditions, the expression of EMT markers, METTL3, and m6A methylation levels were significantly increased in cells(P&#x003C;0.05). Furthermore, the migratory ability of cells was higher in high-sugar medium than in low-sugar medium. In human lens anterior capsules, METTL3 expression was higher in patients with diabetic cataract compared to those with age-related cataract. Importantly, treatment with the METTL3 inhibitor STM2457 inhibited EMT in cells, the expression of TGFβ1 and SNAIL, as well as m6A methylation levels in cells(all P&#x003C;0.05)compared to high-sugar + dimethyl sulfoxide(DMSO)group. Moreover, the migratory capacity of cells was reduced after the addition of STM2457 compared to the high-sugar + DMSO group.CONCLUSION:METTL3 promotes the EMT in human lens epithelial cells under high glucose conditions by activating the TGFβ1/SNAIL pathway, thus contributing to the development of diabetic cataracts.

17.
Acta Pharmaceutica Sinica ; (12): 1024-1032, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978772

RESUMO

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.

18.
Neuroscience Bulletin ; (6): 138-162, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971541

RESUMO

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.


Assuntos
Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Transtornos da Consciência/etiologia , Lesões Encefálicas/complicações , Estado de Consciência , Neuroimagem
19.
Acta Pharmaceutica Sinica B ; (6): 54-67, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971706

RESUMO

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

20.
Chinese Journal of Cardiology ; (12): 731-741, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984711

RESUMO

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.


Assuntos
Humanos , Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Anticoagulantes , Infarto do Miocárdio/complicações , Hemorragia , Intervenção Coronária Percutânea , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral
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