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1.
Mater Today Bio ; 25: 100984, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38356962

RESUMO

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

2.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3650-3663, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37474997

RESUMO

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.


Assuntos
Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Humanos , Medicamentos sem Prescrição/uso terapêutico , Metanálise em Rede , Glomerulonefrite Membranosa/tratamento farmacológico , Teorema de Bayes , Cápsulas , Preparações de Ação Retardada , Medicamentos de Ervas Chinesas/efeitos adversos , Comprimidos
3.
Phytochemistry ; 213: 113745, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37277012

RESUMO

Nine undescribed diterpenoids, euphlactenoids A-I (1-9), including four ingol-type diterpenoids (1-4) with a 5/3/11/3-tetracyclic framework and five ent-pimarane-type diterpenoids (5-9), together with thirteen known diterpenoids (10-22), were identified from the leaves and stems of Euphorbia lactea Haw. The structures and absolute configurations of compounds 1-9 were unequivocally elucidated on the basis of spectroscopic analysis, ECD calculations and single crystal X-ray diffraction. Compounds 3 and 16 showed anti-HIV-1 effects with IC50 values of 1.17 µM (SI = 16.54) and 13.10 µM (SI = 1.93), respectively.


Assuntos
Diterpenos , Euphorbia , HIV-1 , Euphorbia/química , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Abietanos
4.
Dev Cell ; 57(22): 2533-2549.e7, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-36413948

RESUMO

Heart development is controlled by a complex transcriptional network composed of transcription factors and epigenetic regulators. Mutations in key developmental transcription factor MESP1 and chromatin factors, such as PRC1 and cohesin components, have been found in human congenital heart diseases (CHDs), although their functional mechanism during heart development remains elusive. Here, we find that MESP1 interacts with RING1A/RING1, the core component of PRC1. RING1A depletion impairs human cardiomyocyte differentiation, and cardiac abnormalities similar to those in patients with MESP1 mutations were observed in Ring1A knockout mice. Mechanistically, MESP1 associates with RING1A to activate cardiogenic genes through promoter-enhancer interactions regulated by cohesin and CTCF and histone acetylation mediated by p300. Importantly, CHD mutations of MESP1 significantly affect such mechanisms and impair target gene activation. Together, our results demonstrate the importance of MESP1-RING1A complex in heart development and provide insights into the pathogenic mechanisms of CHDs caused by mutations in MESP1, PRC1, and cohesin components.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Cardiopatias Congênitas , Camundongos , Animais , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Organogênese , Diferenciação Celular , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Cardiopatias Congênitas/genética , Camundongos Knockout
5.
Front Cardiovasc Med ; 9: 864312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061535

RESUMO

Objective: At present, there is no early prediction model of left ventricular reverse remodeling (LVRR) for people who are in cardiac arrest with an ejection fraction (EF) of ≤35% at first diagnosis; thus, the purpose of this article is to provide a supplement to existing research. Materials and methods: A total of 109 patients suffering from heart attack with an EF of ≤35% at first diagnosis were involved in this single-center research study. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, with analysis features including demographic characteristics, diseases, biochemical data, echocardiography, and drug therapy. Extreme gradient boosting (XGBoost), random forest, and logistic regression algorithm models were used to distinguish between LVRR and non-LVRR cases and to obtain the most important features. Results: There were 47 cases (42%) of LVRR in patients suffering from heart failure with an EF of ≤35% at first diagnosis after optimal drug therapy. General statistical analysis and machine learning methods were combined to exclude a number of significant feature groups. The median duration of disease in the LVRR group was significantly lower than that in the non-LVRR group (7 vs. 48 months); the mean values of creatine kinase (CK) and MB isoenzyme of creatine kinase (CK-MB) in the LVRR group were lower than those in the non-LVRR group (80.11 vs. 94.23 U/L; 2.61 vs. 2.99 ng/ml; 27.19 vs. 28.54 mm). Moreover, AUC values for our feature combinations ranged from 97 to 94% and to 87% when using the XGBoost, random forest, and logistic regression techniques, respectively. The ablation test revealed that beats per minute (BPM) and disease duration had a greater impact on the model's ability to accurately forecast outcomes. Conclusion: Shorter disease duration, slightly lower CK and CK-MB levels, slightly smaller right and left ventricular and left atrial dimensions, and lower mean heart rates were found to be most strongly predictive of LVRR development (BPM).

6.
Se Pu ; 40(9): 817-824, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36156628

RESUMO

Plant components from extracts of Sophora flavescens, rhodiola, ginseng, Centella asiatica, and tea play important roles in skin whitening, moisturizing, anti-aging, sun protection, anti-inflammation, antiseptic, bacteriostatic, and other effects of cosmetics. At present, no relevant standard methods have been established to detect the addition amounts of plant extracts in cosmetics. In addition, plant extracts listed in product labels may be undetectable due to their addition in trace quantities and the lack of technical support. Therefore, a quantitative method for the simultaneous determination of 22 functional components in cosmetics was established by ultra-high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ/Orbitrap MS). Target compounds were extracted with methanol from samples using ultrasonic extraction, and then separated on a C18 column (100 mm × 2.1 mm, 1.8 µm) with gradient elution of 0.1% (v/v) formic acid aqueous solution (A) and acetonitrile (B). The gradient elution program were as follows: 0-5 min, 5%B-8%B; 5-25 min, 8%B-60%B; 25-35 min, 60%B-80%B; 35-36 min, 80%B-5%B; 36-45 min, 5%B. The flow rate was 0.3 mL/min and the injection volume was 5 µL. Accurate masses of precursor ions were used to detect cosmetic functional components in positive ionization mode. The fragment ions obtained by higher energy collisional dissociation were used for confirmation of the functional components. Each compound showed good linearity. The limits of detection (LODs) were in the range of 0.003-2.01 mg/kg, and the limits of quantification (LOQs) were in the range of 0.02-4.36 mg/kg. Recoveries at three levels were 63.2%-125.1%, and relative standard deviations (RSDs) were 0.18%-10.9%. Fifty-four batches of samples labeled with four monomer functional components and nine plant extracts were tested. In the 17 batches of samples labeled with nicotinamide, 4 batches labeled with caffeine, and 6 batches labeled with Sophora flavescens root extract, the labeled functional components were detected. One out of 11 batches of samples labeled with D-panthenol was not detected. Three of the seven batches of samples labeled with ascorbyl glucoside were not detected. In the 21 batches of samples labeled with licorice extracts, the corresponding functional components were not detected in 9 batches. In the 21 batches of samples labeled with Centella asiatica extract, the corresponding functional components were not detected in 11 batches. In the 13 batches of samples labeled with tea extract, the corresponding functional components were not detected in 8 batches. In 11 of the 12 batches containing ginseng root extract, the corresponding functional components were not detected. In five of the six batches of astragalus membranaceus root extract samples, the corresponding functional components were not detected. In samples labeled with Polygonum cuspidatum root extract, Rehmannia glutinosa root extract, and Ophiopogon japonicus root extract, the corresponding functional components were detected. The method is simple, rapid, reliable, accurate, and suitable for the determination of the 22 functional components in cosmetics.


Assuntos
Anti-Infecciosos Locais , Cosméticos , Acetonitrilas/análise , Anti-Infecciosos Locais/análise , Cafeína/análise , Cromatografia Líquida de Alta Pressão , Cosméticos/análise , Glucosídeos , Íons , Espectrometria de Massas , Metanol/análise , Niacinamida/análise , Extratos Vegetais , Chá
7.
Arch Toxicol ; 96(12): 3245-3255, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36040703

RESUMO

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.


Assuntos
Alcaloides , Antirreumáticos , Ratos , Animais , Distribuição Tecidual , Cromatografia Líquida , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Anti-Inflamatórios , Analgésicos
8.
Orthop Surg ; 13(1): 260-266, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33448672

RESUMO

OBJECTIVE: Venous thromboembolism (VTE) is a significant concern post total joint arthroplasty (TJA). However, the optimal prevention method of VTE remains controversial at present. This study aims to evaluate a risk-stratified VTE prophylaxis protocol for patients undergoing TJA. METHODS: A total of 891 TJA patients from January 2011 to November 2019 were retrospectively investigated. The study was divided into two cohorts. In cohort 1, 410 patients (250 females and 160 males, mean age 64.32 years) were treated with an aggressive VTE chemoprophylaxis protocol. In cohort 2, 481 patients were treated with a risk-stratified protocol that utilized low molecular weight heparins (LMWH) and sequential aspirin (ASA) for standard-risk patients (a total of 288 containing 177 females and 111 males, mean age 65.4 years), and targeted anticoagulation for high-risk patients (a total of 193 containing 121 females and 72 males, mean age 66.8 years). The patients were followed up at 2-4 weeks for an initial visit and at 6-10 weeks for a subsequent visit after surgery. A chart review of all patient medical records was performed to record the demographics, comorbidities, deep vein thrombosis, pulmonary embolus, superficial infection, deep infection, bleeding complications, and 90-day readmissions. RESULTS: The VTE rate was 1.71% (7/410) in cohort 1 and 1.46% (7/481) in cohort 2 respectively. For cohort 2, the VTE rate was 2.07% (4/193) in high-risk group and 1.04% (3/288) in standard-risk group. The readmission rate was 2.44% (10/410) in cohort 1 and 2.08% (10/481) in cohort 2. For cohort 2, the readmission rate was 2.07% (4/193) in high-risk group and 2.08% (6/288) in standard-risk group. The reasons for readmission were as follows: infection, 1.3% (5/410) in cohort 1 and 1.3% (6/481) in cohort 2; wound or bleeding complications, 0.48% (2/410) in cohort 1 and 0.2% (1/481) in cohort 2; trauma, 0.2% (1/410) in cohort 1 and 0.2% (1/481) in cohort 2; VTE, 0.2% (1/410) in cohort 1 and 0.2% (1/481) in cohort 2; others, 0.2% (1/410) in cohort 1 and 0.6% (3/481) in cohort 2. There was a decrease in VTE events and readmissions in the risk-stratified cohort, although this did not reach statistical significance. However, it was found that there was a significant reduction in costs (P < 0.001) with the use of LMWH/ASA, when compared with aggressive anticoagulation agents in the risk-stratified cohort. CONCLUSION: The use of LMWH/ASA in a risk-stratified TJA population is a safe and cost-effective method of VTE prophylaxis.


Assuntos
Artroplastia de Substituição , Aspirina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/uso terapêutico , Quimioprevenção , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos
9.
Mol Oncol ; 15(4): 1234-1255, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33512745

RESUMO

Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, tube formation and co-culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR-145-5p; besides, the NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating the VEGFR-2 signaling pathway via SERPINE1.


Assuntos
Inibidor 1 de Ativador de Plasminogênio/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neovascularização Patológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular
10.
Orthop Surg ; 13(1): 145-152, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33305484

RESUMO

OBJECTIVE: To examine the accuracy, reliability, and reproducibility of a simple preoperative planning technique using plain X-rays. METHODS: A retrospective analysis of 96 consecutive cases of primary direct anterior approach (DAA)-total hip arthroplasty (THA) from July 2015 to December 2018 was performed. The 96 patients included 24 males and 72 females, with an average age of 70 years. The standard AP pelvis radiographs with the patients' hips extended and internally rotated were obtained pre- and postoperatively. The preoperative planning was also completed on the standardized AP pelvic radiographs. The prearranged cup positioning was radiologically measured intraoperatively using fluoroscopy. The correct leg length was assessed intraoperatively, which was compared with the preoperative planning. The component positioning was measured by three independent researchers. Two of the researchers completed the measurements three times, and intra-observer and inter-observer reliability were calculated. All patients received at least 6 months follow-up (6 months-4 years). RESULTS: In all cases, the median leg length discrepancy (LLD) was 4.4 mm (range 1.6-15.9 mm), and 84 patients had an LLD smaller than 10 mm, of which 58 patients had an LLD of less than 5 mm. None of the patients had a critical LLD of 2 cm or larger. The multivariable logistic regression for LLD (safe range: yes/no) with the co-variables including gender, ASA classification, type of cup, the surgeon's experience level, and the presence of a total hip arthroplasty (THA) on the contralateral side did not present statistical significance. The median angle of the inclination of the acetabular component (IA) was 42.3° (range: 28.7°-52.2°). Ninety-one patients were within the defined safe range. The hit ratio for the cup to be within the safe zone was significantly higher for the Pinnacle cups than that for the Continuum cups (P < 0.05). However, there was no significant difference in gender, ASA classification, the surgeon's experience level, and the presence of a total hip arthroplasty (THA) on the contralateral side. The median of its anteversion (AA) was 20.6° (range: 10.6°-40.1°). Only 41 patients were within the defined safe range. None of the co-variables presented a statistical significance affecting the AA of the cup positioning. Meanwhile, the average fluoroscopy time for the cup positioning (n = 86, missing data in 10 cases) was 4 seconds (range: 1-74), with most of the patients (97.9%) having a fluoroscopy time of fewer than 20 seconds. CONCLUSIONS: The combination of correct preoperative planning and standardized intraoperative measurements can reestablish right leg length and assure the correct cup positioning.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia , Desenho de Prótese , Ajuste de Prótese , Radiografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Período Pré-Operatório , Reprodutibilidade dos Testes , Estudos Retrospectivos
11.
Analyst ; 145(15): 5299-5306, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32677633

RESUMO

Serum/plasma holds promise as an important source of disease-related proteins and even biomarkers in clinical practice. However, the discovery of biomarker candidates in serum/plasma remains challenging. In this study, we constructed an MS strategy that enables the fast and precise quantification of serum biomarkers through coupling a high-throughput scheduled MRM strategy with a stable isotope-labelled (SIL) peptide panel from more than 500 plasma proteins as internal standards. With this strategy, we discovered relevant serum proteins of atherosclerosis (AS), lung cancer (LC) and breast cancer (BC), which can simultaneously recognize these diseases. The results indicate that the powerful strategy we constructed has the potential for serum biomarker screening and disease detection.


Assuntos
Proteínas Sanguíneas , Peptídeos , Biomarcadores , Isótopos , Padrões de Referência
12.
Int Heart J ; 61(2): 263-272, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32132317

RESUMO

This study aims to evaluate the effect of dexmedetomidine (DEX) sedation for relieving anxiety and the incidence of atrial fibrillation (AF) after off-pump coronary artery bypass graft (OPCABG).This randomized, double-blind, controlled trial was conducted on 196 patients who underwent OPCABG in Shandong Provincial Hospital from July 2017 to June 2018. The patients were randomly assigned to two groups, intervention of DEX group and Propofol (PROP) group. Episodes of postoperative AF (POAF) were identified within 5 days after OPCABG. Perioperative anxiety status was assessed using Zung's Self-Rating Anxiety Scale (SAS). The baseline demographic and surgical characteristics of the population and other outcome variables were evaluated.We analyzed 62 patients in the DEX group and 61 patients in the PROP group. There was no significant difference in SAS anxiety scores between two groups before surgery (P = 0.104), while SAS had significantly after surgery (P = 0.018). The incidence of POAF in the DEX group was lower than that of the PROP group (16.1% versus 32.8%, P = 0.037), and a total of 30 patients (30/123, 24.4%) manifested POAF after OPCABG. Some univariable predictors of POAF were detected. The conceptual model of mediator analyses showed DEX was not only directly related to POAF but was also indirectly related through the independent effect of anxiety level.The findings indicated that patients receiving DEX were more likely to have less incidence of POAF, also uniquely showed DEX administration and POAF processes as a function of anxiety status.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Ansiedade/prevenção & controle , Fibrilação Atrial/prevenção & controle , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Dexmedetomidina/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Idoso , Ansiedade/etiologia , Fibrilação Atrial/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
13.
Front Neurol ; 10: 1095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681156

RESUMO

The best results of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) were observed in epilepsies with more limited lesions, but this procedure is rarely used in a wide range of brain malformation. We report a rare case of polymicrogyria (PMG) combined with drug-resistant startle seizures. Presurgical monitoring was performed using SEEG owing to the large lesion and complexity of PMG. According to the intracranial electrode results, the seizure onset was extensive, with the onset starting earlier in the cingulate sulcus and insular pole than in other sites of the other electrodes. Multi-point and multi-step SEEG-guided RF-TC was used for diffuse lesion and functional protection. RF-TC was first applied to the cingulate sulcus and insular pole, and our patient was rendered free from startle seizures after 2 weeks. Two weeks of observation helped us to observe the efficacy of RF-TC and the changes of SEEG, so as to make the next TC scheme. The patient still had spontaneous seizures after the first treatment. RF-TC was then applied to other sites involved earlier. Finally, the patient reached Engel class IIa for a follow-up period of 1 year. There were no additional startle seizures, and important functional areas were protected.

14.
Oncol Lett ; 18(3): 2825-2834, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452761

RESUMO

microRNA (miR/miRNA)-27a-3p has been reported to be abnormally expressed in various types of cancer, including colorectal cancer (CRC). B-cell translocation gene 1 (BTG1) has also been implicated with CRC. However, the association between miR-27a-3p and BTG1 in CRC, to the best of our knowledge, has not been investigated. In order to assess whether miR-27a-3p is associated with CRC, reverse transcription-quantitative PCR was performed on 20 paired CRC and paracancerous tissues for miRNA analysis. For the screening and validation of miR-27a-3p expression in colon cancer, several colon cancer cell lines (HCT-116, HCT8, SW480, HT29, LOVO and Caco2) and the normal colorectal epithelial cell line NCM460 were examined. The highest expression levels of miR-27a-3p were detected in the HCT-116, which was selected for further experimentation. The HCT-116 cells were divided into control, miR-27a-3p mimic and inhibitor groups, and cell proliferation was tested using an MTT assay. Additionally, miR-27a-3p inhibitor/mimic or BTG1 plasmid were transfected into the HCT-116 cells, and flow cytometry was performed to analyze cell cycle distributions. TUNEL analysis was performed to detect apoptosis. Protein levels of factors in the downstream signaling pathway mediated by miR-27a-3p [ERK/mitogen-activated extracellular signal-regulated kinase (MEK)] were detected. miR-27a-3p was revealed to be overexpressed in human CRC tissues and colon cancer cell lines. Knockdown of miR-27a-3p suppressed proliferation of HCT-116 cells and apoptosis was increased. It further markedly upregulated expression levels of BTG1 and inhibited activation of proteins of the ERK/MEK signaling pathway. In addition, overexpression of BTG1 in HCT-116 cells triggered G1/S phase cell cycle arrest and increased apoptosis via the ERK/MEK signaling pathway. In conclusion, the present study demonstrated that the effects of miR-27a-3p on colon cancer cell proliferation and apoptosis were similar to those of the tumor suppressor gene BTG1. The miR-27a-3p/BTG1 axis may have potential implications for diagnostic and therapeutic approaches in CRC.

15.
BMC Neurol ; 19(1): 165, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315594

RESUMO

BACKGROUND: Nowadays, few surgery analysis has been reported in cases of epilepsy after viral encephalitis(VE). Herein, this study was to evaluate the efficacy of surgery and capability of stereoelectroencephalography (SEEG) in the definition of the epileptogenic zone (EZ) after VE, and also to explore the relationship between the SEEG features and the surgical outcomes. METHODS: We retrospectively analyzed 10 surgically treated patients that identified to suffer from epilepsy secondary to VE using SEEG, and investigated the SEEG features associated with surgical outcomes in these patients. Besides visual analysis, we used the epileptogenicity index (EI), a semi-quantitative and supplementary tool to evaluate the validity of SEEG in the context of VE. RESULTS: Among the 10 operated patients, 3 of them became completely seizure-free. The patients who got totally seizure free or significant improvement, the seizure onset was located either in the antero-mesial temporal structures or focal gyrus; patients who got worthwhile improvement or no improvement, the seizure started from multiple brain lobes. The number of electrodes classified as epileptogenic visually involved were closely correlated with EI positive onses.Anatomic areas defined and shown as EZ on MRI by visual assessment were also defined as epileptogenic by the EI in these cases. CONCLUSION: Apart from exploring the surgical outcome related to epilepsy after VE, we also bring insight into the relationship between the SEEG features and surgical outcome with the application of the supplementary methods.


Assuntos
Eletroencefalografia/métodos , Encefalite Viral/complicações , Epilepsia/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Eletrodos , Epilepsia/virologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/cirurgia , Resultado do Tratamento , Adulto Jovem
16.
Vet Parasitol ; 262: 56-74, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30389013

RESUMO

Species of Gasterophilus are obligate parasites of equids and may induce severe, even lethal myiasis. However, identification of the third instar Gasterophilus larva at the species level is still problematic predominantly due to a shortage of diagnostic morphological features and incomplete molecular libraries. Testing the suitability of three different molecular markers showed that the traditional 650 bp barcode region near the 5' terminus of the cytochrome c oxidase subunit I (COI) served as a better tool for species-level identification than a 663 bp region near the 3' terminus of COI and a 554 bp region near the 5' terminus of the large subunit ribosomal RNA. We found that barcoding discriminates G. intestinalis, G. nasalis, G. nigricornis and G. pecorum but not G. haemorrhoidalis and G. inermis. A comparative morphological study using scanning electron microscopy was conducted to promote the identification of the third instar larvae. Photographs of fresh mature third instar larvae are provided for all species, and the remarkable green body colour of third instar G. nigricornis is fully documented for the first time. Two morphological keys are provided, one is suitable for quick identification, and the other based on ultrastructural details is provided for further comparative morphological investigation. A new term 'oral plate' instead of 'mandible' was proposed for a pair of sclerites of uncertain homology emerging from the secondary mouth opening. Our data shows that DNA barcodes cannot replace morphology for identification of third instars of Gasterophilus species, and a scaffold is provided for an integrated taxonomic reference system, which will contribute to monitoring gasterophilosis for equid welfare and protection, and also facilitate further studies in functional anatomy, phylogenetic analyses and host-parasite co-evolutionary investigations of Gasterophilus.


Assuntos
Dípteros/classificação , Doenças dos Cavalos/parasitologia , Miíase/veterinária , Animais , Código de Barras de DNA Taxonômico/veterinária , Dípteros/genética , Dípteros/ultraestrutura , Feminino , Cavalos , Larva , Masculino , Miíase/parasitologia , Filogenia , Estômago/parasitologia
17.
Yi Chuan ; 40(10): 900-915, 2018 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-30369472

RESUMO

Gene editing is a technology for precision modification of genome sequences or expressing transcripts. Early versions of such techniques include homing endonuclease, zinc finger endonuclease and transcription-like activator effectors. The CRISPR/Cas9 system has recently emerged as a powerful and versatile gene editing tool for a broad spectrum of applications. In this review, we discuss the recent development and applications of gene editing technology, and particularly focus on the progress in China, with the emphasis on mechanistic studies, development of new and extended technologies, the applications in animals, plants and the therapeutics.


Assuntos
Animais Geneticamente Modificados/genética , Edição de Genes , Plantas Geneticamente Modificadas/genética , Animais , Sistemas CRISPR-Cas , China , Engenharia Genética , Pesquisa/tendências
18.
Zhongguo Gu Shang ; 31(10): 912-915, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30373343

RESUMO

OBJECTIVE: To explore occurrence and risk factors of sarcopenia in patients with hip facture. METHODS: From May 2013 to January 2017, 187 patients with hip fractures were collected, including 99 males and 88 females aged from 50 to 95 years old with an average age of (77.40±10.58) years old. General conditions, appendicular skeletal muscle index (ASMI), total fat mass, bone mineral content (BMC), body mass index (BMI), grip strength, preoperative blood vitamin D (VITD), albumin, American Society of Anesthesiologists(ASA) classification and new mobility scores(NMS) were observed and analyzed. According to grip strength and ASMI, patients were divided into sarcopina group and non-sarcopina group, univariate and multivariate statistical methods were used to analyzed. RESULTS: Ninty-nine patients(52.9%) were diagnosed as sarcopenia. Compared with non-sarcopenia group, occurrence of sarcopenia was associated with advanced age, high ASA, low total fat mass, low bone mineral content, low BMI, low albumin, and low NMS. Subsequent binary logistic regression analysis showed that advanced age (OR=1.804, P=0.048), high ASA score (OR=3.052, P=0.001), low fat content (OR=0.843, P=0.006), low bone mineral salt(OR=0.203, P=0.026) were risk factors of hip fracture patient with sarcopenia. CONCLUSIONS: Old age, high ASA score, low fat content, low bone mineral content may be related risk factors for sarcopenia in hip fracture patients.


Assuntos
Fraturas do Quadril , Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Biomed Environ Sci ; 27(11): 907-11, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25374025

RESUMO

This study was conducted to elucidate the reproductive effect of NP on testis, epididymis and epididymal sperm in vivo. Adult male Sprague-Dawley rats were gavaged with NP at 0, 40, 100, or 250 mg/kg body weight (bw) on alternate days for 90 d. The results showed that oral administration of NP may damage the structure and function of testis, induce apoptosis and oxidative stress in epididymis or even have cytotoxic effects on epididymal sperm.


Assuntos
Epididimo/efeitos dos fármacos , Fenóis/efeitos adversos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epididimo/metabolismo , Epididimo/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue
20.
Neuroimage ; 101: 473-84, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25067815

RESUMO

Structural and functional connectomes are emerging as important instruments in the study of normal brain function and in the development of new biomarkers for a variety of brain disorders. In contrast to single-network studies that presently dominate the (non-connectome) network literature, connectome analyses typically examine groups of empirical networks and then compare these against standard (stochastic) network models. The current practice in connectome studies is to employ stochastic network models derived from social science and engineering contexts as the basis for the comparison. However, these are not necessarily best suited for the analysis of connectomes, which often contain groups of very closely related networks, such as occurs with a set of controls or a set of patients with a specific disorder. This paper studies important extensions of standard stochastic models that make them better adapted for analysis of connectomes, and develops new statistical fitting methodologies that account for inter-subject variations. The extensions explicitly incorporate geometric information about a network based on distances and inter/intra hemispherical asymmetries (to supplement ordinary degree-distribution information), and utilize a stochastic choice of network density levels (for fixed threshold networks) to better capture the variance in average connectivity among subjects. The new statistical tools introduced here allow one to compare groups of networks by matching both their average characteristics and the variations among them. A notable finding is that connectomes have high "smallworldness" beyond that arising from geometric and degree considerations alone.


Assuntos
Conectoma/métodos , Modelos Estatísticos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
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