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1.
Int Orthop ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513549

RESUMO

PURPOSE: Hallux valgus is a common disease which causes pain and dysfunction of the foot. Although numerous methods of procedures have been introduced, a single procedure cannot correct all deformities of hallux valgus. The study aims to evaluate the radiographic and clinical effectiveness of a new minimally invasive surgery (MIS) versus open Chevron-Akin procedures. METHODS: This was a retrospective comparative study. Data were collected from May 2018 to January 2020. A total of 27 patients (31 feet) undergoing MIS for hallux valgus were included in this study. The average age of patients underwent MIS was 59.9 years. The mean follow-up was 25.1 months. Open osteotomies were performed in 30 patients (31 feet) during the same period. The mean age of these patients at the time of surgery was 59.1 years. The mean follow-up was 26.1 months. Pre-operative and post-operative radiographic outcome measures included HVA, IMA, DMAA, the Sgarlato's angle and the length of the first metatarsal, and distance between the dorsal cortex of first and second metatarsal necks. The AOFAS and VAS were used to assess foot function. RESULTS: The preoperative HVA in MIS group and open group were 34.8° and 33.1° respectively. The post-operative HVA were 20.4° and 13.7°. The pre-operative IMA in MIS group and open group were 13.0° and 12.1°. The post-operative IMA were 11.4° and 5.5° respectively. The pre-operative DMAA were 14.8° and 15.1° respectively. The post-operative DMAA were 6.3° and 8.7°. The AOFAS increased from 44.0 to 90.2 in MIS group and from 47.6 to 89.5 in open group. The VAS decreased from 7.3 to 1.3 in MIS group and from 7.1 to 1.2 in open group. CONCLUSION: Although open osteotomies were superior than MIS in HVA and IMA, MIS showed advantages in correcting DMAA. MIS provided equivalent functional outcomes compared to open surgery.

2.
Cancer Biol Med ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35535966

RESUMO

Lung cancer is associated with a heavy cancer-related burden in terms of patients' physical and mental health worldwide. Two randomized controlled trials, the US-National Lung Screening Trial (NLST) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON), indicated that low-dose CT (LDCT) screening results in a statistically significant decrease in mortality in patients with lung cancer, LDCT has become the standard approach for lung cancer screening. However, many issues in lung cancer screening remain unresolved, such as the screening criteria, high false-positive rate, and radiation exposure. This review first summarizes recent studies on lung cancer screening from the US, Europe, and Asia, and discusses risk-based selection for screening and the related issues. Second, an overview of novel techniques for the differential diagnosis of pulmonary nodules, including artificial intelligence and molecular biomarker-based screening, is presented. Third, current explorations of strategies for suspected malignancy are summarized. Overall, this review aims to help clinicians understand recent progress in lung cancer screening and alleviate the burden of lung cancer.

3.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1824-1830, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534252

RESUMO

Leaf blight outbroke in Rehmannia glutinosa plantation in Wenxian county, Henan province in 2019. R. glutinosa plants with diseased leaves were collected from the plantation, and three strains were isolated from the diseased leaf samples. Pathogenicity test, morphological observation, and phylogenetic analysis of ITS, EF1-α, and Tub suggested that they were respectively Fusarium proliferatum, F. oxysporum, and F.acuminatum. Among them, F. acuminatum, as a pathogen of R. glutinosa leaf disease, had never been reported. To clarify the biological characteristics of F. acuminatum, this study tested the influence of light, pH, temperature, medium, carbon source, and nitrogen source on the mycelial growth rate of the pathogen during a 5-day culture period, and explored the lethal temperature. The results showed that the mycelia grew well under the photoperiod of 12 h light/12 h darkness, at 5-40 ℃(optimal temperature: 25 ℃), at pH 4-11(optimal pH: 7.0), on a variety of media(optimal medium: oatmeal agar), and in the presence of diverse carbon and nitrogen sources(optimal carbon source: soluble starch; optimal nitrogen source: sodium nitrate). The lethal temperature was verified to be 51 ℃(10 min). The conclusion is expected to lay a scientific basis for diagnosis and control of R. glutinosa leaf diseases caused by F. acuminatum.


Assuntos
Rehmannia , Carbono , Nitrogênio , Filogenia
4.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556763

RESUMO

Learning and memory-related behaviors depend on GPCR signaling to the nucleus to induce Immediate early gene (IEG) expression. However, the molecular mechanisms mediating this process remain unclear. We have previously identified a subpopulation of ß2 AR which is preferentially phosphorylated by GRK sites and internalized to the endosome upon stimulation. Here, we demonstrate that GRK phosphorylated endosomal ß2 Adrenergic Receptor (ß2 AR) indirectly facilitates nuclear cAMP signaling through sequestration of a PDE4D/ß-arrestin complex. Combining subcellular cAMP biosensors and transgenic mice, we found deleting GRK phosphorylation sites on ß2 AR (GRKD) blocked agonist-induced receptor endocytosis and nuclear cAMP signaling in hippocampal neurons. This resulted in impaired PKA-mediated IEGs expression in vitro,reduced learning induced IEG expression in vivo, and impaired long-term memory in a Morris water maze. Mechanistically, while ß2 AR stimulation promoted ß-arrestin-dependent recruitment of PDE4D5, inhibition of ß-arrestin-PDE4D5 association alone prevented ß2 AR-induced increases in nuclear cAMP signaling without affecting receptor endocytosis. Furthermore, direct PDE4 inhibition was sufficient to rescue the ß2 AR-induced nuclear cAMP signal in GRKD neurons and ameliorate the long-term memory deficits in GRKD mice. This work indicates that the sequestration of the ß-arrestin/PDE4D complex by the GRK-phosphorylated ß2 AR critically controls the receptor-induced nuclear cAMP signals. This constitutes a novel mechanism by which GPCR activation promotes nuclear cAMP signaling through endocytosis dependent relocalization of PDE4D isoforms, IEG expression, and learning and memory-related behaviors.

5.
Chin J Integr Med ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508859

RESUMO

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

6.
BMC Cardiovasc Disord ; 22(1): 215, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35546659

RESUMO

BACKGROUND: This study aimed to explore clinical value and expression of Homer 1, S-adenosyl-l-homocysteine (SAH), homocysteine (Hcy), fibroblast growth factors (FGF) 23 in coronary heart disease (CHD). METHODS: From March 2020 to April 2021, a total of 137 patients with CHD and 138 healthy subjects who came to our hospital for physical examination and had no cardiovascular disease were retrospectively enrolled, and they were assigned to the CHD group and the control group, respectively. Patients in the CHD group were divided into stable angina pectoris (SAP) group (n = 48), unstable angina pectoris (UAP) group (n = 46), and acute myocardial infarction (AMI) group (n = 43) according to clinical characteristics for subgroup analysis. The degree of coronary artery stenosis was assessed by Gensini score, which is a reliable assessment tool for the severity of coronary artery disease. The levels of Homer 1, SAH, Hcy, and FGF 23 were tested and compared. Spearman correlation analysis was used to analyze the correlation between serum Homer1, SAH, Hcy, FGF23 levels and Gensini score, and multivariate unconditional Logistic regression was used to analyze the risk factors of coronary heart disease. RESULTS: Demographic characteristics of each group were comparable (P > 0.05). The body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and glucose levels of the SAP group, UAP group and AMI group were significantly higher than those of the control group, and the number of patients with smoking, alcohol consumption, hypertension, and diabetes history was significantly more than that of the control group, respectively (P < 0.05). The level of high-density lipoprotein cholesterol (HDL-C) of each subgroup was significantly lower than the control group (P < 0.05). The above indicators showed no significant difference among three subgroups (P > 0.05). Serum SAH, Hcy, Homer1 and FGF23 levels in each subgroup were significantly higher than those in control group (P < 0.05). And above indicators in SAP group and UAP group were significantly lower than those in AMI group (P < 0.05), and the levels of above indicators in SAP group were significantly lower than those in UAP group (P < 0.05). The results of Spearman correlation analysis showed that serum Homer1, FGF23, SAH, Hcy levels were positively correlated with Gensini score (r = 0.376, 0.623, 0.291, 0.372, all P < 0.01). Multivariate logistic regression analysis showed that smoking, hypertension, diabetes, alcohol consumption, obesity, HDL-C, FGF23, SAH, Hcy, Homer 1 were independent risk factors for coronary heart disease. CONCLUSION: The levels of FGF23, SAH, Hcy, and Homer1 tend to increase in patients with CHD compared with normal population, and the more severe the disease, the higher the levels, which has certain reference value for the clinical diagnosis of CHD and the evaluation and monitoring of the disease.

7.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35555990

RESUMO

Increasing biased G-protein coupled receptor (GPCR) drugs are now under clinical investigation. More understanding of the biased ß-adrenergic receptor (ß-AR) signaling is urgently required for a better cardiovascular drug. Here we found that two nitric oxide synthase (NOS) isotypes, NOS1, and NOS3 coupled with ß1ARs and transduce distinct ß1AR-cGMP signaling at sarcoplasmic reticulum and myofilament microdomain, respectively. Intriguingly, activation of NOS1 enhanced contractility and Ca2+ cycling, whereas NOS3 promoted contraction without affecting intracellular Ca2+ . Quantitative proteomic revealed that NOS3 activation increased phosphorylation of myosin proteins including myosin binding protein C (MyBP-C), myosin light chain kinase (MYLK) and myosin phosphatase target subunit 1 (MYPT1), to enhance contractility by Ca2+ sensitization. Moreover, in heart failure, excessive adrenergic stimulation dissociated ß1AR from NOS1 and impaired the NOS1-cGMP signaling. Accordingly, stimulating NOS3 but NOS1 enhances systolic cardiac contraction in failing mice without rousing intracellular Ca2+ . We propose NOS facilitate biased ß1AR-cGMP signaling via Ca2+ -dependent or independent mechanisms and define NOS3-cGMP as specific therapeutic strategy targeting myofilament for heart failure.

8.
Front Neurol ; 13: 861184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557620

RESUMO

Background and Purpose: To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD). Methods: An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated. Results: Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group. Conclusions: These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.

9.
Front Pharmacol ; 13: 863588, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559243

RESUMO

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120-160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60-80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04076371.

10.
Bioorg Chem ; 124: 105817, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35490583

RESUMO

Natural products are mainly secondary metabolites produced by plants, microorganisms, and animals, which are still abundant in modern drug discovery. Terpenoids are the most diverse group of natural products, attracting extensive attention owing to their various biological activities. This manuscript reviewed the chemical structures, anti-inflammatory activities, and mechanisms of action of 281 terpenoid natural products reported from 2010 to the present. Their biological targets and both in vitro and in vivo screening models were also surveyed and statistically summarized. This review will provide potential anti-inflammatory lead compounds and helpful information to researchers engaged in natural products and anti-inflammatory drug discovery.

12.
Ageing Res Rev ; 77: 101619, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35395415

RESUMO

As the number of patients with Alzheimer's disease (AD) increases, it brings great suffering to their families and causes a heavy socioeconomic burden to society. A vast amount of funds and a mass of research have been devoted to elucidating the pathology of AD. However, the main pathogenesis is still elusive, and its mechanism is not completely clear. Research on the mechanisms of AD mainly focuses on the amyloid cascade, tau protein, neuroinflammation, metal ions, and oxidative stress hypotheses. Oxidative stress is as a bridge that connects the different hypotheses and mechanisms of AD. It is a process that causes neuronal damage and occurs in various pathways. Oxidative stress plays a critical role in AD and can even be considered a crucial central factor in the pathogenesis of AD. Previous reviews have also summarized the role of oxidative stress in AD, but these mainly review a specific signaling pathway. Taking oxidative stress as the central point, this review comprehensively expands on the roles of oxidative stress that are involved in the pathogenesis of AD. The vivid and easy-to-understand figures systematically clarify the connected roles of oxidative stress in AD and allow readers to further understand oxidative stress and AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Humanos , Metais , Estresse Oxidativo/fisiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-35451482

RESUMO

BACKGROUND: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth-factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large vessel occlusive disease on the microcirculation within human kidneys. METHOD: This study included 5 patients who underwent nephrectomy due to renovascular occlusion, and 7 non-stenotic discarded donor kidneys (4 deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression, and histology were studied in-vitro using immunoblotting, polymerase-chain-reaction, and staining. RESULTS: RAS demonstrated loss of medium-sized vessels (0.2-0.3mm) compared to donor kidneys (p = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor (HIF)-1α, and thrombospondin (TSP)-1, but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTC) and pericyte detachment were greater in RAS, yet they had more newly-formed PTC than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the post-stenotic human kidney. RAS induced renal microvascular loss, vascular remodeling, and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. CONCLUSIONS: These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis, and support therapeutic strategies directly targeting the post-stenotic kidney microcirculation in patients with RAS.

14.
Technol Cancer Res Treat ; 21: 15330338221085354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422168

RESUMO

Background: The role of N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) in osteosarcoma (OS) has not been fully studied yet. We aimed to identify m6A-related lncRNAs that could act as prognostic biomarkers for OS. Methods: Pearson correlation was performed to identify m6A-related lncRNAs. Univariate and multivariate Cox regression analyses were performed to construct the risk model and assess whether the risk score was an independent prognostic factor for patients with OS. Gene Set Enrichment Analysis (GSEA) was performed to analyze the functions of genes in high-risk and low-risk groups. StarBase and Cytoscape were used to construct a competing endogenous RNA (ceRNA) network based on m6A-related prognostic lncRNA signature. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of genes involved in the ceRNA network. Results: We extracted 122 common lncRNAs from TCGA and Gene Expression Omnibus (GEO) databases. Pearson correlation results revealed 59 significant m6A-related lncRNAs in The Cancer Genome Atlas (TCGA) database, from which 2 were screened to construct a risk signature in TCGA dataset, which was then validated in the GEO dataset. A corresponding risk score was calculated and shown to be an independent prognostic factor for patients with OS. Enrichment analysis indicated that cell proliferation-related biological processes were more common in the high-risk group, while immune-related biological processes were more common in the low-risk group. Moreover, we established a nomogram that had a good ability to predict the overall survival of patients with OS. Additionally, a ceRNA network based on small nucleolar RNA host gene 7 (SNHG7) and small nucleolar RNA host gene 12 (SNHG12) was constructed, with genes that were enriched in hepatocellular carcinoma, gastric cancer, and non-small-cell lung cancer pathways. Conclusion: Our study revealed the prognostic role of m6A-related lncRNAs in OS and identified SNHG7 and SNHG12 as potential biomarkers for predicting the prognosis of patients with OS. These findings have enriched our understanding of the role of m6A modification in the dysregulation of lncRNAs in OS.


Assuntos
Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Osteossarcoma , RNA Longo não Codificante , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/genética , Humanos , Osteossarcoma/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Nucleolar Pequeno
15.
Front Cell Infect Microbiol ; 12: 836987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425720

RESUMO

Objective: There is evidence that the gut microbiota play a regulatory role in the occurrence and progression of tuberculosis. The purpose of the current study was to explore the alterations in gut microbiome under different tuberculosis disease stages in the Uyghur population, clarify the composition of microbial taxonomy, search for microbial biomarkers and provide innovative ideas for individual immune prevention and for control strategies. Design: A case-control study of Uyghur individuals was performed using 56 cases of pulmonary tuberculosis (PTB), 36 cases of latent tuberculosis infection (LTBI) and 50 healthy controls (HC), from which stool samples were collected for 16S rRNA gene sequencing. Results: The results showed that the alpha diversity indexes of the PTB group were lower than those of the other two groups (P <0.001), while only observed species were different between LTBI and HC (P <0.05). Beta diversity showed differences among the three groups (P = 0.001). At the genus level, the relative abundance of Bifidobacterium and Bacteroides increased, while Roseburia and Faecalibacterium decreased in the PTB group, when compared with the other two groups, but the changes between the LTBI and HC groups were not significant. The classifier in the test set showed that the ability of the combined genus to distinguish between each two groups was 81.73, 87.26, and 86.88%, respectively, and the validation efficiency was higher than that of a single screened genus. Conclusion: The gut microbiota of PTB patients was significantly disordered compared with LTBI and HC, while the changes of LTBI and HC were not significant. In the future, gut microbiota could be used as a non-invasive biomarker to assess disease activity.


Assuntos
Microbioma Gastrointestinal , Tuberculose Latente , Tuberculose Pulmonar , Tuberculose , Biomarcadores , Estudos de Casos e Controles , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética , Tuberculose Pulmonar/microbiologia
16.
Front Public Health ; 10: 835810, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419334

RESUMO

The flipped classroom (FC) teaching has been increasingly employed in medical education. Many studies have shown this "student-centered" pedagogical model improves students' overall achievement in the course, with students showing more motivation and better self-directed learning skills when compared to the traditional classroom teaching. However, most of the previous studies have been evaluating the short-term effects of FC teaching conducted upon completion of the course. The retention of the promotion and the long-term effects on learning of students' subsequent courses deserve further attention and evaluation. By adopting and running FC teaching in the whole course of physiology, this study aimed to determine the short-term impact of FC teaching on students' learning of physiology course and also the long-term influences in students' learning of follow-up medical curriculums within 18 months after the completion of physiology course. 119 sophomore students majoring in clinical medicine from Central South University were recruited and they were assigned randomly into two groups: the control group (n =61) who received the traditional lecture (TL) teaching, and the experimental group (n =58), who received the FC teaching. In this study, students' final exam scores were used to assess their learning effectiveness and an independent samples t-test was conducted to compare scores between the two groups. Our study showed that FC teaching significantly improved the learning outcome of physiology in the experimental group compared with the control group (P = 0.0001) without obvious impact on the learning of other subjects conducted in the same period of time. Moreover, our results also demonstrated the long-term benefit of FC teaching, with students from the experimental group scoring higher in pathophysiology (P = 0.006), pathology (P = 0.029), pharmacology (P = 0.0089), diagnostics (P = 0.01) and internal medicine (P = 0.0004) than those from the control group. The study results indicate that FC is a promising teaching approach to increase students' learning effectiveness in physiology course, and the long-term effects of FC facilitate the learning of the follow-up medical courses. Furthermore, this study also demonstrates that although the time investment on physiology is increased by FC teaching, it does not weaken students' learning of other courses conducted in the same period of time.


Assuntos
Educação Médica , Estudantes de Medicina , Currículo , Humanos , Aprendizagem , Aprendizagem Baseada em Problemas/métodos
18.
Oncogene ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468938

RESUMO

Epithelial ovarian cancer (EOC) is classified into five major histotypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC), and mucinous (MOC). However, the landscape of molecular and immunological alterations in these histotypes, especially LGSOC, CCOC, ENOC, and MOC, is largely uncharacterized. We collected 101 treatment-naive EOC patients. The resected tumor tissues and paired preoperative peripheral blood samples were collected and subjected to target sequencing of 1021 cancer-associated genes and T cell repertoire sequencing. Distinct characteristics of mutations were identified among the five histotypes. Furthermore, tumor mutation burden (TMB) was found to be higher in CCOC and ENOC, but lower in LGSOC and HGSOC. Alterations associated with DNA damage repair (DDR) pathways and homologous recombination deficiencies (HRD) were prevalent in five histotypes. CCOC demonstrated increased level of T cell clonality compared with HSGOC. Interestingly, the proportion of the 100 most common T cell clones was associated with TMB and tumor neoantigen burden in CCOC, highlighting more sensitive anti-tumor responses in this histotype, which was also evidenced by the enhanced convergent recombination of T cell clones. These findings shed light on the molecular traits of genomic alteration and T cell repertoire in the five major EOC histotypes and may help optimize clinical management of EOC with different histotypes.

19.
Gynecol Oncol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35469684

RESUMO

OBJECTIVE: To evaluate the oncological and reproductive outcomes in patients with seromucinous borderline ovarian tumors (SMBOT) treated with fertility-sparing surgery (FSS). METHODS: We retrospectively reviewed the medical records of patients with SMBOT who underwent surgery between 2000 and 2019. A centralized histological review was performed and recurrence rates were compared between different surgical procedures. RESULTS: A total of 105 patients fulfilled the inclusion criteria, of whom 65 underwent FSS and 40 were treated with radical surgery (RS). Fourteen patients had recurrent disease after a median follow-up time of 59.6 months (range: 22.1-256.8 months). All but one relapsed with SMBOT. There was no significant difference in disease-free survival (DFS) between the two groups (P = 0.141). Multivariate analysis showed that only bilateral involvement was associated with increased recurrence (P = 0.008). In the subgroup of patients treated with conservative surgery, there was no significant difference in DFS with regard to surgical procedures (ovarian cystectomy vs salpingo-oophorectomy, P = 0.487). Of the 12 patients in the FSS group who developed recurrence, 11 underwent a second round of FSS and all remained alive with no evidence of disease at the end of follow-up. Of 20 patients desiring pregnancy, 16 patients were successful and resulted in 17 term deliveries. CONCLUSIONS: FSS is feasible for young patients who wish to preserve their fertility. Patients initially treated with ovarian cystectomy may be managed by close surveillance if post-operative imaging are negative. Repeat FSS remains a valuable alternative for young patients with recurrent SMBOT after thorough communication.

20.
IEEE Trans Cybern ; PP2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476561

RESUMO

Evolving Android malware poses a severe security threat to mobile users, and machine-learning (ML)-based defense techniques attract active research. Due to the lack of knowledge, many zero-day families' malware may remain undetected until the classifier gains specialized knowledge. The most existing ML-based methods will take a long time to learn new malware families in the latest malware family landscape. Existing ML-based Android malware detection and classification methods struggle with the fast evolution of the malware landscape, particularly in terms of the emergence of zero-day malware families and limited representation of single-view features. In this article, a new multiview feature intelligence (MFI) framework is developed to learn the representation of a targeted capability from known malware families for recognizing unknown and evolving malware with the same capability. The new framework performs reverse engineering to extract multiview heterogeneous features, including semantic string features, API call graph features, and smali opcode sequential features. It can learn the representation of a targeted capability from known malware families through a series of processes of feature analysis, selection, aggregation, and encoding, to detect unknown Android malware with shared target capability. We create a new dataset with ground-truth information regarding capability. Many experiments are conducted on the new dataset to evaluate the performance and effectiveness of the new method. The results demonstrate that the new method outperforms three state-of-the-art methods, including: 1) Drebin; 2) MaMaDroid; and 3) N-opcode, when detecting unknown Android malware with targeted capabilities.

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