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1.
Cell Discov ; 10(1): 70, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937452

RESUMO

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

2.
Nat Commun ; 15(1): 5300, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906860

RESUMO

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.


Assuntos
Docetaxel , Resistencia a Medicamentos Antineoplásicos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Piroptose , Ubiquitina-Proteína Ligases , Ubiquitinação , Humanos , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Piroptose/efeitos dos fármacos , Piroptose/genética , Ubiquitinação/efeitos dos fármacos , Animais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos , Camundongos Nus , Feminino , Dinaminas/metabolismo , Dinaminas/genética , Espécies Reativas de Oxigênio/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/genética , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fosforilação/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Pessoa de Meia-Idade , Gasderminas
3.
Artigo em Inglês | MEDLINE | ID: mdl-38547516

RESUMO

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation (AF). During follow-up after 9 to 24 weeks of Rivaroxaban treatment, patients were divided into 'effective group' (n = 143) and 'ineffective group' (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAADmean), angle between left atrial appendage and left atrial (LAA-A), velocity of blood flow in left atrial appendage (LAA-v) and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF and LAA-v values were greater and LAD and LAADmean values were lower in the effective (P<0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A and LAA-v with anticoagulant efficacy (P<0.05). The efficacy of Rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A and LAA-v. Multivariate logistic regression analysis further revealed LAEF (OR 1.7, 95% CI 0.45-16.9, P=0.008), 3D-EF (OR 6.4, 95% CI 1.06-16.9, P=0.039), and left ventricular global longitudinal strain (GLS) (OR 18.0, 95% CI 1.38-35.68, P=0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of Rivaroxaban as an anticoagulation agent.

4.
Clin Interv Aging ; 19: 219-227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352273

RESUMO

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.


Assuntos
Norepinefrina , Procedimentos Cirúrgicos Operatórios , Idoso , Humanos , Estudos de Coortes , Norepinefrina/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos , Infecções Urinárias/complicações
5.
Fertil Steril ; 121(6): 937-945, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38272383

RESUMO

OBJECTIVE: To compare the live birth rate of the first frozen embryo transfer (FET) after ovarian stimulation by the progestin-primed ovarian stimulation (PPOS) protocol vs. the antagonist protocol in women with an anticipated high ovarian response who were undergoing in vitro fertilization. DESIGN: Randomized controlled trial. SETTING: A tertiary assisted reproduction center. PATIENTS: Women with infertility aged <43 years undergoing the first in vitro fertilization cycle and having antral follicle count of >15. INTERVENTIONS: Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS protocol. In the antagonist protocol, an antagonist 0.25 mg daily was given from the sixth day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. MAIN OUTCOME MEASURE: Live birth rate of the first FET cycle. RESULTS: A total of 784 women were recruited from June 2020 and October 2021 and assigned randomly in a 1:1 ratio into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 women (62/392, 15.8%) in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no FET within 6 months after randomization. The two groups were similar in demographic characteristics and the numbers of oocytes obtained or fertilized, cleaving embryos, good-quality embryos at day 3, blastocysts developed, and embryos or blastocysts frozen. There was no statistically significant difference in the live birth rate of the first FET cycle between the PPOS and antagonist groups on the basis of both the intention-to-treat analysis (37.5.0% [147/392] vs. 32.7% [128/392]; relative risk, 1.148 [95% confidence interval, 0.949-1.390]) and per-protocol analysis (44.5% [147/330] vs. 39.1% [128/327]; relative risk, 1.138 [95% confidence interval, 0.950-1.364]). Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, and cumulative live birth rates. CONCLUSION: The live birth rates of the first FET following the PPOS and antagonist protocols were comparable in women with an anticipated high ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT04414761 (ClinicalTrials.gov).


Assuntos
Criopreservação , Transferência Embrionária , Nascido Vivo , Indução da Ovulação , Progestinas , Humanos , Feminino , Indução da Ovulação/métodos , Transferência Embrionária/métodos , Adulto , Gravidez , Nascido Vivo/epidemiologia , Progestinas/administração & dosagem , Fertilização in vitro/métodos , Coeficiente de Natalidade , Taxa de Gravidez , Antagonistas de Hormônios/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/efeitos adversos , Resultado do Tratamento
6.
Huan Jing Ke Xue ; 44(12): 6529-6540, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098381

RESUMO

Brown carbon (BrC) refers to a group of organic compounds in fine atmospheric particles (PM2.5) that are able to absorb light in the ultraviolet and visible range. They have a significant impact on the visibility of air and on the earth's climate. In this study, we used a black carbon analyzer (Model AE33) to conduct field measurements in northern suburban Nanjing from March 2021 to February 2022. We measured the light absorption coefficients of BrC in PM2.5 and quantified the contributions of primary (BrCpri) and secondary brown carbon (BrCsec) in BrC by using the minimum correlation method (MRS), combined with the backward trajectories,potential source contribution function (PSCF) analysis, and diurnal patterns to analyze the seasonal characteristics of BrC. The results showed that the annual average light absorption of BrC was(7.76±7.17)Mm-1 (at 370 nm), and its contribution to the total aerosol light absorption was (22.0±8.8)%. BrC light absorption at different wavelengths all showed a U-shape seasonal variation of high in spring and winter and low in summer and fall. MRS analysis showed that the annual average contributions of BrCpri and BrCsec were (62.9±21.4)% and (37.1±21.4)% (at 370 nm), respectively; however, the contribution of BrCsec increased with the increase in wavelength, and it became dominant in longer wavelengths such as 660 nm. Backward trajectory and PSCF analysis showed that BrC was heavily influenced by air masses from the sea in spring, summer, and fall but was influenced greatly by local and regional continental emissions in winter. Traffic emissions in spring, summer, and fall were more intense to contribute to BrCpri than that in winter, whereas coal and biomass combustion had a greater impact on BrCpri in winter. Detailed analysis revealed that gas-phase photochemistry and aqueous chemistry had different influences on BrCsec formation in different seasons. It was mainly from gas-phase photochemistry in summer but was dominated by aqueous process in winter; both processes, however, were important pathways to BrCsec in spring and fall.

7.
Org Biomol Chem ; 21(37): 7530-7534, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37674373

RESUMO

Carbamoyl-Hantzsch esters were used as carbamoyl radical precursors for oxidative carbamoylation of N-arylacrylamides and N-arylcinnamamides in the presence of inexpensive persulfates. This protocol can be applied to a broad range of substrates with various functional groups, providing a variety of 3,3-disubstituted oxindoles and 3,4-disubstituted dihydroquinolin-2(1H)-ones in moderate to good yields via an intermolecular addition/cyclization process.

8.
Perioper Med (Lond) ; 12(1): 4, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890549

RESUMO

BACKGROUND: Dexamethasone is commonly used for antiemesis in surgical patients. It has been confirmed that long-term steroid use increases blood glucose level in both diabetic and non-diabetic patients, it is unclear how a single dose of intravenous dexamethasone used pre/intraoperatively for postoperative nausea and vomiting (PONV) prophylaxis would influence the blood glucose and wound healing in diabetic patients. METHODS: The Pubmed, Cochrane Library, Embase, Web of Science databases, CNKI and Google Scholar were searched. The articles reporting a single dose dexamethasone administered intravenously for antiemesis in surgical patients with diabetes mellitus (DM) were included. RESULTS: Nine randomized controlled trials (RCTs) and 7 cohort studies were included in our meta-analysis. The results showed that dexamethasone increased glucose level intraoperatively (MD: 0.439, 95% CI: 0.137-0.581, I2 = 55.7%, P = 0.004), at the end of surgery (MD: 0.815, 95% CI: 0.563-1.067, I2 = 73.5%, P = 0.000), on postoperative day (POD) 1 (MD: 1.087, 95% CI: 0.534-1.640, I2 = 88%, P = 0.000), on POD 2 (MD: 0.501, 95% CI: 0.301-0.701, I2 = 0%, P = 0.000), and increased peak glucose level within 24 hours of surgery (MD: 2.014, 95% CI: 0.503-3.525, I2 = 91.6%, P = 0.009) compared with control. It indicated that dexamethasone caused the increase of perioperative glucose level at different time points by 0.439 to 1.087 mmol/L (7.902 to 19.566 mg/dL), and the increase of peak glucose level within 24 hours of surgery by 2.014 mmol/L (36.252 mg/dL) compared with control. Dexmethasone had no impact on wound infection (OR: 0.797, 95%CI: 0.578-1.099, I2 = 0%, P = 0.166) and healing (P < 0.05). CONCLUSION: Dexamethasone could increase blood glucose by only 2.014 mmol/L (36.252 mg/dL) of peak glucose level within 24 hours of surgery in surgery patients with DM, the increase of glucose level at each time point perioperatively was even lower, and had no effect on wound healing. Thus, dexamethasone with a single dose could be safely used for PONV prophylaxis in diabetic patients. TRIAL REGISTRATION: The protocol of this systematic review was registered in INPLASY with the registration number INPLASY202270002.

9.
J Cardiothorac Vasc Anesth ; 36(12): 4393-4402, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36155718

RESUMO

OBJECTIVES: To develop and validate a nomogram for predicting postoperative pulmonary infection (PPI) in patients undergoing lung surgery. DESIGN: Single-center retrospective cohort analysis. SETTING: A university-affiliated cancer hospital PARTICIPANTS: A total of 1,501 adult patients who underwent lung surgery from January 2018 to December 2020. INTERVENTIONS: Observation for PPI within 7 days after lung surgery. MEASUREMENTS AND MAIN RESULTS: A complete set of demographics, preoperative variables, and postoperative follow-up data was recorded. The primary outcome was PPI; a total of 125 (8.3%) out of 1,501 patients developed PPI. The variables with p < 0.1 in univariate logistic regression were included in the multivariate regression, and multivariate logistic regression analysis showed that surgical procedure, surgical duration, the inspired fraction of oxygen in one-lung ventilation, and postoperative pain were independent risk factors for PPI. A nomogram based on these factors was constructed in the development cohort (area under the curve: 0.794, 95% CI 0.744-0.845) and validated in the validation cohort (area under the curve: 0.849, 95% CI 0.786-0.912). The calibration slope was 1 in the development and validation cohorts. Decision curve analysis indicated that when the threshold probability was within a range of 0.02-to-0.58 and 0.02-to-0.42 for the development and validation cohorts, respectively, the nomogram model could provide a clinical net benefit. CONCLUSIONS: The authors developed and validated a nomogram for predicting PPI in patients undergoing lung surgery. The prediction model can predict the development of PPI and identify high-risk groups.


Assuntos
Neoplasias Pulmonares , Nomogramas , Adulto , Humanos , Estudos Retrospectivos , Pulmão , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
10.
Chem Asian J ; 16(24): 4087-4094, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34668333

RESUMO

This work reports the photocatalytic application of an anthraquinone-containing polymeric photosensitizer (AQ-PHEMA) in the visible light-induced cross-dehydrogenative-coupling of N-aryl tetrahydroisoquinolines with several nucleophiles, including nitromethane, 1-methyl-2-alkyl ketone and dialkyl (aryl) phosphine oxide. The results revealed that the reaction could be catalyzed by AQ-PHEMA efficiently to afford a series of 1-substituted-2-aryl-1,2,3,4-tetrahydroisoquinolines in good to excellent yields with nice substrate tolerance under aerobic conditions at room temperature. The practical application potential was also showcased by a gram-scale synthesis. More importantly, the utilization of AQ-PHEMA as a heterogeneous photosensitizer also showed nice recyclability and reusability of the catalyst, whereas AQ-PHEMA can be easily separated and reused for at least 8 times without significant loss of photocatalytic activity.

11.
Org Lett ; 23(15): 6153-6157, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34269587

RESUMO

An efficient visible-light-promoted N-radical-mediated tandem radical cyclization/defluorinated alkylation of ß,γ-unsaturated hydrazones, and α-trifluoromethyl alkenes is described. This protocol provides a general and effective route to synthesize various dihydropyrazole-fused gem-difluoroalkenes at moderate to excellent yields under redox-neutral, metal-free, and mild conditions.

12.
Org Lett ; 22(4): 1542-1546, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31989828

RESUMO

In this study, a facile and efficient method to synthesize monofluoroalkenes by photoredox catalytic defluorinative alkylation of gem-difluoroalkenes with 4-alkyl-1,4-dihydropyridines under mild conditions (room temperature) is described. This novel strategy is applicable for a broad range of gem-difluoroalkene substrates with good functional group tolerance and a variety of 4-alkyl-1,4-dihydropyridines (including primary, secondary, and even tertiary alkyl radicals). Moreover, it also allows the challenging radical coupling with glycosyl-based 4-alkyl-1,4-dihydropyridines (DHPs) to synthesize monofluoroalkenylated saccharides.

13.
Front Oncol ; 10: 625184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33552995

RESUMO

PURPOSE: To assess the impact of comorbidity on treatment outcomes in patients with locally recurrent nasopharyngeal carcinoma (lrNPC) using intensity-modulated radiotherapy (IMRT) and to develop a nomogram that combines prognostic factors to predict clinical outcome and guide individual treatment. METHODS: This was a retrospective analysis of patients with lrNPC who were reirradiated with IMRT between 2003 and 2014. Comorbidity was evaluated by Adult Comorbidity Evaluation-27 grading (ACE-27). The significant prognostic factors (P < 0.05) by multivariate analysis using the Cox regression model were adopted into the nomogram model. Harrell concordance index (C-index) calibration curves were applied to assess this model. RESULTS: Between 2003 and 2014, 469 lrNPC patients treated in our institution were enrolled. Significant comorbidity (moderate or severe grade) was present in 17.1% of patients by ACE-27. Patients with no or mild comorbidity had a 5-year overall survival (OS) rate of 36.2 versus 20.0% among those with comorbidity of moderate or severe grade (P < 0.0001). The chemotherapy used was not significantly different in patients with lrNPC (P > 0.05). For the rT3-4 patients, the 5-year OS rate in the chemotherapy + radiation therapy (RT) group was 30.0 versus 16.7% for RT only (P = 0.005). The rT3-4 patients with no or mild comorbidity were associated with a higher 5-year OS rate in the chemotherapy + RT group than in the RT only group (32.1 and 17.1%, respectively; P=0.003). However, for the rT3-4 patients with a comorbidity (moderate or severe grade), the 5-year OS rate in the chemotherapy + RT group vs. RT alone was not significantly different (15.7 vs. 15.0%, respectively; p > 0.05). Eight independent prognostic factors identified from multivariable analysis were fitted into a nomogram, including comorbidity. The C-index of the nomogram was 0.715. The area under curves (AUCs) for the prediction of 1-, 3-, and 5-year overall survival were 0.770, 0.764, and 0.780, respectively. CONCLUSION: Comorbidity is among eight important prognostic factors for patients undergoing reirradiation. We developed a nomogram for lrNPC patients to predict the probability of death after reirradiation and guide individualized management.

14.
CNS Neurosci Ther ; 25(9): 951-964, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31486601

RESUMO

AIMS: The objective of this study was to analyze the efficacy of polypyrrole/polylactic acid (PPy/PLA) nanofibrous scaffold cotransplanted with bone marrow stromal cells (BMSCs) in promoting the functional recovery in a rat spinal cord injury (SCI). METHODS: Female Sprague-Dawley rats were randomly divided into three groups (n = 18/group): control group, PPy/PLA group, and PPy/PLA/BMSCs group. The SCI was induced in all rats. Consequently, rats in PPy/PLA/BMSCs group were transplanted with 1 × 105 BMSCs after implantation of PPy/PLA, while those in the PPy/PLA group were implanted with PPy/PLA only; no implantation was performed in the control group. Six weeks after surgery, immunofluorescence microscopy, electron microscope, and polymerase chain reaction (PCR) techniques were performed to assess the changes in the injured spinal cord tissues. RESULTS: Electrophysiology and locomotor function testing suggested that PPy/PLA nanofibrous scaffold cotransplanted with BMSCs could promote the functional recovery of the spinal cord. Six weeks after the operation, lower amount of scar tissue was found in the PPy/PLA group compared with the control group. Abundant neurofilament (NF) and neuron-specific marker (NeuN) positive staining, and myelin formations were detected in the injured area. In addition, the transplantation of BMSCs not only improved the efficacy of PPy/PLA but also managed to survive well and was differentiated into neural and neuroglial cells. CONCLUSIONS: The implantation of PPy/PLA nanofibrous scaffold and BMSCs has a great potential to restore the electrical conduction and to promote functional recovery by inhibiting the scar tissue formation, promoting axon regeneration, and bridging the gap lesion.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Nanofibras/administração & dosagem , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapia , Alicerces Teciduais , Animais , Células Cultivadas , Feminino , Poliésteres/administração & dosagem , Polímeros/administração & dosagem , Pirróis/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia
15.
World J Clin Cases ; 6(13): 600-610, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30430115

RESUMO

AIM: To investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases. METHODS: This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05. RESULTS: Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis). CONCLUSION: Iron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

16.
Org Lett ; 20(17): 5126-5129, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30125120

RESUMO

Rhodium(III)-catalyzed remote meta-selective-C-H alkenylation of phenol derivatives has been developed using a traceless organosilicon template as the directing group. This transformation proceeds smoothly with good yields and high meta-selectivities toward a series of phenol and alkene substrates. In addition, this protocol provides an effective strategy for late-stage transformations of various meta-alkenylated aromatic compounds.

17.
Opt Lett ; 43(2): 341-344, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29328276

RESUMO

We report a passively mode-locked erbium-doped fiber laser with pulse widths switchable from 473 fs to 76.8 ns, where the fundamental mode-locking, noise-like pulse, nanosecond mode-locking, and dual-width mode-locking (DML) are obtained by adjusting a polarization controller. Co-existence of femto- and nano-second pulses in DML is attributed to the gain balancing. Analytic modeling of the fiber laser with the cubic-quintic Ginzburg-Landau equation is presented, in which the pulse widths are calculated as functions of dispersion, self-phase modulation (SPM), cubic saturable absorption (SA), and quintic SA. The generation of nanosecond pulses is caused by the weakened intracavity pulse-shortening strength, the reduced effective SPM, and the inclusion of quintic SA in the laser cavity.

18.
Aging Ment Health ; 21(3): 241-252, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26362821

RESUMO

OBJECTIVES: Spouse caregivers have been the predominant family members who care for persons with dementia in Taiwan. Although studies in western countries have described the caregiving experiences and changes in the marital relationship for these spouse caregivers, this information is lacking in Taiwan. This study explored the experiences of spouse caregivers caring for persons with dementia in Taiwan. METHODS: A grounded theory approach was used for this qualitative descriptive study. Data were collected through recorded in-depth interviews and observations with 15 spouse caregivers of persons with dementia. Constant comparative analysis was used to analyse the transcripts and field notes. RESULTS: Analysis of interview transcripts revealed that the experiences of caregiving for spouse caregivers who lived with persons with dementia could be described as 'progressive compensatory symbiosis.' This core category included three components: awareness of unbalanced intimacy, making a commitment and implementing a compensatory scheme. These experiences could be either mutually beneficial or unbalanced and fluctuated as the disease progressed through the phases of 'subtle,' 'revealed' and 'confirmed,' which also influence the pace, transition and evolution of the compensatory symbiosis. CONCLUSION: This exploratory study describes the family caregiving experiences for 15 spouse caregivers of persons with dementia in Taiwan. These results can provide guidance for developing interventions to prepare, facilitate and promote a mutually beneficial adjustment for spousal caregivers and their spouses as dementia progresses. The findings are worthy of further investigation with a larger sample and a prospective design.


Assuntos
Cuidadores/psicologia , Demência/enfermagem , Cônjuges/psicologia , Atividades Cotidianas , Idoso , Empatia , Feminino , Teoria Fundamentada , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estresse Psicológico/psicologia , Taiwan
19.
Oncotarget ; 8(12): 20371-20379, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27901494

RESUMO

We sought to comprehensively assess the efficacy of Intermittent Pneumatic Compression (IPC) in patients undergoing gynecologic surgery. A computerized literature search was conducted in Pubmed, Embase and Cochrane Library databases. Seven randomized controlled trials involving 1001 participants were included. Compared with control, IPC significantly lowered the deep vein thrombosis (DVT) risk [risk ratio (RR) = 0.33, 95% confidence interval (CI): 0.16 - 0.66]. The incidence of DVT in IPC and drugs group was similar (4.5% versus. 3.99%, RR = 1.19, 95% CI: 0.42 - 3.44). With regards to pulmonary embolism risk, no significant difference was observed in IPC versus control or IPC versus drugs. IPC had a lower postoperative transfusion rate than heparin (RR = 0.53, 95% CI: 0.32 - 0.89), but had a similar transfusion rate in operating room to low molecular weight heparin (RR = 1.06, 95% CI: 0.69 - 1.63). Combined use of IPC and graduated compression stockings (GCS) had a marginally lower risk of DVT than GCS alone (RR = 0.38, 95% CI: 0.14 - 1.03). In summary, IPC is effective in reducing DVT complications in gynecologic surgery. IPC is neither superior nor inferior to pharmacological thromboprophylaxis. However, whether combination of IPC and chemoprophylaxis is more effective than IPC or chemoprophylaxis alone remains unknown in this patient population.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Dispositivos de Compressão Pneumática Intermitente , Tromboembolia Venosa/prevenção & controle , Feminino , Humanos
20.
Opt Lett ; 40(4): 483-6, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25680130

RESUMO

Stable optical pulse trains are obtained from 1.3-µm and 1.5-µm semiconductor optical amplifier (SOA)-based fiber lasers using passive optical technology. The waveforms depend on SOA currents, and the repetition rates can be tuned by varying the relative length of sub-cavities. The output pulse trains of these SOA-based fiber lasers are stable against intracavity polarization adjustment and environmental perturbation. The optical clock generation is explained in terms of mode competition, self-synchronization, and SOA saturation. Without resorting to any active modulation circuits or devices, the technology used here is simple and may find various applications in the future.


Assuntos
Amplificadores Eletrônicos , Lasers Semicondutores , Fibras Ópticas , Fenômenos Ópticos
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