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1.
Neuroradiology ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242265

RESUMO

PURPOSE: Data on posterior circulation tandem occlusions in acute ischemic stroke are scarce: recognition may be challenging and little is known about optimal treatment strategy. We report our endovascular treatment strategy for posterior circulation tandem occlusion. METHODS: Consecutive patients with posterior circulation tandem occlusions in our centre were enrolled retrospectively. The preferred strategy was "distal-to-proximal" strategy, which means opening the distal occlusion first followed by treatment of the proximal pathology. The imaging characteristics, treatment strategy, clinical outcomes, and complications of patients with posterior circulation tandem occlusions were analyzed. RESULTS: In total, 21 patients with posterior circulation tandem occlusions were enrolled in the study, which accounted for 23.6% of patients with posterior circulation stroke in our centre. The mean age was 60 years (range 32 to 80), and median pre-procedure NIHSS score was 28 (interquartile range: 13-31). Eighteen patients (85.7%) had vertebrobasilar artery tandem occlusions and 3 (14.3%) had basilar artery to basilar artery tandem occlusions. All distal occlusions were successfully recanalized (modified TICI 2b/3). Two (9.5%) of the proximal lesions were not treated. A total of 57.1% of the patients had stents implanted on the proximal occlusions. The rate of mRS 0-3 at 3 months was 57.1% and the mortality rate was 19.0%. CONCLUSION: In patients with acute ischaemic stroke caused by posterior circulation tandem occlusions, we favor "distal-to-proximal" strategy based on the positive results in this small series. Nevertheless, a more extensive study is required to explore the optimal treatment strategy further.

2.
Int J Hematol ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32162095

RESUMO

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) represent a promising treatment option for EBV-associated post-transplantation lymphoproliferative disorders (PTLD). However, production of EBV-CTLs is often complicated and expensive. In the present study, we sought to establish an easy-to-use and economical production protocol for EBV-CTLs. EBV-CTLs were generated using latent membrane protein 1 (LMP1) peptides based on a modified generation protocol of cytokine-induced killer (CIK) cells. After 2-week culture, cells were well expanded (median total cell number: 9.82 × 109; median expansion fold: 107.8) and the median EBV LMP1-specific CD8+ T cell number was 8.94 × 108 (median frequency: 6.7%). However, the EBV-CTL products, unlike CIK cells, did not exhibit NK-like anti-tumor activity. Furthermore, the clinical efficacy of EBV-CTLs was demonstrated with a successful treatment of PTLD on a compassionate use basis in a patient following haploidentical hematopoietic stem cell transplantation. This study indicates the safety and efficacy of EBV LMP1-specific CTLs generated based on a modified generation protocol of CIK cells. Further investigation in a well-designed clinical study is warranted.

3.
Urol Oncol ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199754

RESUMO

BACKGROUND: Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD. MATERIALS AND METHODS: A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients. RESULTS: Acr-dG levels were statistically correlated with CKD stages in UC patients (P < 0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P < 0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P < 0.005). CONCLUSION: These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

4.
PLoS One ; 15(3): e0229341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150552

RESUMO

Very poor reclaimed soil quality and weak microbial activity occur in the reclamation area of a coal gangue landfill in the Loess Hills. The fourth and fifth years after farmland soil was reclaimed were studied, and the changes in and carbon source utilization characteristics of rhizosphere (R) and non-rhizosphere (S) soil microorganisms under organic and inorganic (OF), inorganic (F), and organic (O) fertilizer application and a control treatment (CK) in soybean (S) and maize (M) rotation systems were compared and analysed in Guljiao Tunlan, Shanxi Province, China. Biolog-EcoPlate technology was used to analyse the mechanism of soil characteristic change from the perspective of soil microbial metabolism function to provide a theoretical basis for reclamation and ecological reconstruction in this area. The average well colour development (AWCD) absorption and Shannon-Wiener index values of soybean and maize rhizosphere microorganisms were higher than those of non-rhizosphere microorganisms, and the mean value of the fertilizer treatment was higher than that for CK. Principal component analysis shows the main carbon sources that impact the functional diversity of the soybean rhizosphere and non-rhizosphere soil communities are a-cyclodextrin, a-D-lactose, ß-methyl D-glucoside, and glucose-1-phosphate and L-phenylalanine, while those for the maize rhizosphere and non-rhizosphere soil communities are D-cellobiose, glucose-1-phosphate, ß-methyl D-glucoside, methyl pyruvate, D-galactosate gamma lactone, D-mannitol, N-acetyl-D-glucosamine, D-galactosalonic acid, and L-serine. The comprehensive utilization score of the non-rhizosphere soil carbon source in the maize season increased with respect to that in the soybean season, and the maximum increase was 1.09 under the OF treatment. Redundancy analysis showed that the soil nutrient factors driving the changes in the metabolic function diversity index values of the rhizosphere and non-rhizosphere soil microbial communities in the different crop seasons in the reclamation area differed, but they were all related to the soil organic matter and available phosphorus. This may explain why OF treatment is the most beneficial to soil fertility under the rotation system in mining reclamation areas.

6.
J Formos Med Assoc ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32081564

RESUMO

BACKGROUND/PURPOSE: The inflammatory milieu has been firmly established to affect cancer progression. However, the connection between natural killer (NK) cells and prostate cancer (PCa) has not been elucidated. METHODS: Prospective data on NK cell activity (NKA) and NK cell subset distribution patterns were evaluated from 51 patients treated with robot-assisted laparoscopic radical prostatectomy. Whole-blood samples were collected from patients preoperatively and 4-6 weeks postoperatively. The samples were subjected to NKA tests, NK cell number counts, determination of the NKG2D (activating receptor of NK cells), NKG2A (inhibiting receptor), and other surface markers. All the analyses were compared to the clinicopathological characteristics of patients. NKA was estimated by measuring interferon-γ (IFN-γ) levels after stimulation of the peripheral blood with PROMOCA™, which specifically stimulates the release of IFN-γ from NK cells. RESULTS: NKA was lower in patients with PCa than in healthy participants (484.66 vs. 1550 pg/mL). A paired comparison revealed significantly higher NKA postoperatively than preoperatively (1054 vs. 484.66 pg/mL; p = 0.011). Patients with negative surgical margins exhibited significantly higher postoperative NKA and NKA ratio (postoperative NKA/preoperative NKA) than those with positive margins (557 vs. 1921 pg/mL, p < 0.001; 3.6 vs. 1.59, p = 0.024). However, there was no difference in the postoperative NK cell number or the CD56bright/CD16-/CD3- or CD56dim/CD16+/CD3- cell numbers between the negative and positive margin groups. Postoperative NKA was significantly higher in lower-stage (1/2) than in higher-stage (3/4) PCa (1365 vs. 594 pg/mL, p = 0.014). CONCLUSION: NKA was significantly higher postoperatively than preoperatively. Patients with positive surgical margins had lower postoperative NKA than those with negative margins. Lower postoperative NKA was also observed in higher-stage PCa. NKA could be used as a supplemental marker for detecting the remaining tumor cells after prostatectomy in combination of PSA.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32006721

RESUMO

Although nebulized corticosteroids (NebCS) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aims to clarify the role of NebCS in children aged ≤5 years for the management of acute asthma exacerbations, asthma maintenance therapy and for the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children aged ≤5 years, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of ≥40 participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCS to be at least as efficacious as oral corticosteroids in the emergency room (ER) for the management of mild-to-moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCS are effective and well tolerated in patients aged ≤5 years for the management of acute and chronic asthma.

8.
Drug Des Devel Ther ; 14: 429-434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099327

RESUMO

Background: Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases. Aim: The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism. Methods: Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: No significant differences were observed for omeprazole and midazolam, compared to the control group. T max and t1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (T max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001). Conclusion: Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32088665

RESUMO

Context: Cervical spondylosis (CS) is a very common, age-related, chronic, disc-degeneration condition. Alternative medicine has been widely used to treat neck pain in CS. However, no randomized controlled trials have focused on the effects and safety of percutaneous neuromuscular electrical stimulation (PNMES) for neck-pain relief in patients with CS. Objective: The study aimed to evaluate the effects and safety of PNMES for treating neck pain in patients with cervical spondylosis (CS). Design: The research team designed a two-arm, double-blinded, randomized, sham-controlled trial. Setting: The study was conducted at the People's Hospital of Yan'an in Yan'an, China. Participants: Participants were 124 patients with neck pain from CS at the hospital. Intervention: Participants were randomly divided into an intervention group and a control group in a ratio of 1:1. The intervention group received PNMES (PNMES group), and the control group received sham PNMES for 30 minutes daily 3 times weekly, for 12 weeks. Outcome Measures: The outcome measures included: (1) a visual analog scale (VAS), (2) a test of cervical range of motion (ROM), and (3) the neck disability index (NDI) score. All outcome measurements were measured immediately postintervention and in a follow-up at 4 weeks postintervention. In addition, AEs were also recorded duration the period of treatment. Results: Immediately postintervention and at the follow-up, the PNMES group exhibited decreases in the mean VAS (P < .01) and NDI score (P < .01) that were significantly greater than those of the control group. Additionally, the increase in the mean ROM was significantly higher in the PNMES group than that in the control group, both immediately postintervention and at the follow-up (P < .01). No AEs were found in either group. Conclusions: The results of this study have demonstrated that PNMES is more effective than sham PNMES for neck-pain relief in patients with CS.

10.
World J Urol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060632

RESUMO

OBJECTIVES: The purpose of this study is to screen bladder cancer-associated biomarkers by combining lncRNA, miRNA, and mRNA expression profile of bladder cancer, and to explore bladder cancer-associated tumor markers by constructing a ceRNA regulation network. METHODS: Bladder cancer mRNA and miRNA samples were downloaded from the TCGA database; the lncRNA and mRNA detected in the RNA-seq expression profile were identified using the HUGO Gene Nomenclature Committee database. RESULTS: Screening for significant differentially expressed RNA resulted in 1693 mRNAs, 66 lncRNAs, and 130 miRNAs. Then, the significant differently expressed RNAs from the screening were subjected to annotation analysis of GO functional nodes and KEGG signaling pathways. A ceRNA regulation network consisting of lncRNA-miRNA-mRNA was constructed by synthesizing lncRNA-miRNA and miRNA-mRNA. Finally, a ceRNA regulation network consisting of two lncRNAs, one miRNA, and three mRNAs was obtained. KM remodeling curve analysis was performed for each factor. CONCLUSIONS: In bladder cancer tumor samples, samples down-regulated by LINC01198, PPTRD-AS1, has-miR-216a, SEMA3D, EPHA5, and DCLK1 had a good overall survival prognosis, indicating that these several characteristic target molecules were found to be high-risk factors for bladder cancer tumors.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 17-23, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948519

RESUMO

OBJECTIVE: To study the value of body fat mass measured by bioelectrical impedance analysis (BIA) in predicting abnormal blood pressure and abnormal glucose metabolism in children. METHODS: Stratified cluster sampling was used to select the students aged 6-16 years, and a questionnaire survey and physical examination were performed. The BIA apparatus was used to measure body fat mass. Body mass index (BMI), body fat mass index (FMI), and fat mass percentage (FMP) were calculated. Fasting blood glucose level were measured. RESULTS: A total of 14 293 children were enrolled, among whom boys accounted for 49.89%. In boys and girls, the percentile values (P60, P65, P70, P75, P80, P85, P90, P95) of FMI and FMP fitted by the LMS method were taken as the cut-off values. Based on the receiver operating characteristic curve analysis, the P70 values with a better value in predicting abnormal blood pressure and blood glucose metabolism were selected as the cut-off values for excessive body fat. When FMI or FMP was controlled below P70, the incidence of abnormal blood pressure or abnormal glucose metabolism may be decreased in 8.25%-43.24% of the children. CONCLUSIONS: The evaluation of obesity based on FMI and FMP has a certain value in screening for hypertension and hyperglycemia in children, which can be further verified in the future prevention and treatment of obesity and related chronic diseases in children.


Assuntos
Tecido Adiposo , Adolescente , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Criança , Impedância Elétrica , Feminino , Glucose , Humanos , Masculino
13.
Cancer Epidemiol ; 64: 101657, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918180

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) remains the mainstay treatment for locally advanced or metastatic prostate cancer (PC). However, potential effects of ADT treatment on neurocognitive dysfunction remain unclear. The present study was conducted to assess the relation between ADT treatment and risk of cognitive decline in Asian men with PC. METHODS: A population-based cohort of 24,464 men with PC, each newly diagnosed between 2000 and 2008, was selected from the Taiwan National Health Insurance Database. Subjects were further grouped by treatment as non-ADT (n = 4685) or ADT (n = 12,740), members of the latter subjected to bilateral orchiectomy or medical treatment (ie, luteinizing hormone-releasing hormone agonists, antiandrogens, or combination therapy). A multivariable Cox proportional hazard model with ADT as time-dependent covariate was used to generate adjusted hazard ratios (HRs) of subsequent cognitive decline, including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). RESULTS: ADT showed a significant association with overall risk of cognitive decline (HR = 1.51, 95 % CI: 1.31-1.74), especially for PD, dementia, and non-Alzheimer dementia (non-AZD). When stratified by various ADT regimens, antiandrogen-only recipients displayed significantly heightened risks of subsequent AD, non-AZD, and PD. However, combined androgen blockade also imposed an increased risk of PD. There was no apparent correlation between duration of ADT exposure and cognitive dysfunction. CONCLUSIONS: Various ADT therapies may have disparate impacts on cognitive function. Prospective studies exploring pertinent clinical characteristics more fully are needed to confirm these findings.

14.
BMC Surg ; 20(1): 8, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924213

RESUMO

BACKGROUND: To observe if closing the mesenteric defect with absorbable sutures creates a safe adhesion compared to non-absorbable suture after Roux-en-Y gastric bypass. METHODS: Rats were randomly assigned to 5 experimental groups according to the different suture materials used in closing the mesenteric defects (Peterson's space) after Roux-en-Y gastric bypass. Group A (control group), Group B (non-absorbable suture, Prolene suture), Group C (biological glue), Group D (non-absorbable suture, polyester suture) and Group E (absorbable suture). All rats were followed up for 8 weeks postoperatively and underwent laparotomy to observe the degree of adhesion and closure of the mesenteric defect. RESULTS: No significant difference was found in the decrease in food intake and body weight among all groups. No internal hernia (IH) occurred in any group. The mesenteric defects of Group A remained completely visible without any closure or adhesion. Multiple gaps were found between the Prolene suture and the mesentery along the suture line in Group B. The mesenteric defects of Group C were complete closed with multiple adhesions of the small intestine and the greater omentum. The mesenteric defects in both Group D and Group E closed completely. The average adhesion scores in Group A and Group B were 0 and 0.33 ± 0.52 respectively. The average adhesion score in group C (3.83 ± 0.41) was higher than the other groups (p<0.05). The average adhesion scores in Group D and E were similar (3.17 ± 0.41 and 3.00 ± 0.00 respectively). CONCLUSION: Absorbable suture created a safe adhesion score between the mesentery which was not inferior to non-absorbable sutures.

15.
Sci Rep ; 10(1): 776, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964956

RESUMO

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

16.
Chemistry ; 26(6): 1414-1421, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31762095

RESUMO

Charge-transfer (CT) complexes, formed by noncovalent bonding between electron-rich (donor, D) and electron-deficient (acceptor, A) molecules (or moieties) have attracted considerable attention due to their fascinating structures and potential applications. Herein, we demonstrate that anion coordination is a promising strategy to promote CT complex formation between anion-binding, electron-rich tris(urea) donor ligands (D) and electron-deficient viologen cation acceptors (A), which form co-crystals featuring infinite ⋅⋅⋅DADA⋅⋅⋅ or discrete (circular DADA or three-decker DAD) π-stacking interactions. These CT complexes were studied by X-ray diffraction, UV/Vis spectroscopy, electric conductivity measurements, charge displacement curve (CDC) calculations, and DFT computations.

17.
Micron ; 129: 102777, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31811977

RESUMO

Sensilla on antennae of the workers and soldiers of Coptotermes formosanus Shiraki were examined by scanning electron microscopy in this study. As the two castes were allocated totally different tasks in the termite colony, we wondered if there was a big difference between their antennae which were recognized as the main sensory appendages of insects. Therefore, detailed information about the morphology, distribution and abundance of various types of sensilla was described in this report. However, our results showed no obvious caste dimorphism was observed. The morphology of antennae and sensilla as well as the general sensilla distribution pattern did not differ between the workers and soldiers of C. formosanus. In total, seven types of sensilla including sensilla chaetica (I, II, III), Böhm bristles, sensilla campaniformia (I, II, III), sensilla trichodea, sensilla basiconica, sensilla trichodea curvata and sensilla capitula were found on the antennae. Additionally, small apertures were found scattered randomly in the antennal cuticle. Functions of these sensilla or structures were proposed to be mechanoreceptors, chemo-receptors, thermo-hygroreceptors, co2-receptors etc. which probably play crucial roles in their various social behaviors.

18.
Orthop Surg ; 12(1): 124-132, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31849195

RESUMO

OBJECTIVE: To assess the long-term outcomes after percutaneous reduction (PR) and screw fixation versus plate fixation via the sinus tarsi approach (STA) for displaced intra-articular calcaneal fractures (DIACF). METHODS: This retrospective study included a total of 150 patients (June 2008-August 2011), comprising 85 men and 65 women (mean age, 38.4 years), who were assigned to the PR group or the STA group. The inclusion criteria were DIACF (>2 mm) including Sanders type II and III, closed fracture, unilateral fracture, no history of smoking or no smoking during hospitalization and 3 months after surgery, and follow-up time not less than 8 years. The exclusion criteria were clear surgical contraindications (severe cardiovascular and cerebrovascular diseases), local or systemic infection symptoms, diagnosis with diabetes or lower extremity vascular disease, and Sanders type IV or open fractures. Outcomes were assessed by means of the American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scores, radiographic images, and postoperative complications. RESULTS: The mean follow-up period was 8.7 years (range, 8.0-10.0 years). The AOFAS scores in the PR group during the follow-up period were 54.2 ± 5.1, 85.8 ± 4.0, 88.1 ± 3.8, 87.9 ± 3.6, 87.8 ± 3.9, 86.9 ± 3.9, respectively, and in the STA group were 55.0 ± 5.6, 84.5 ± 5.2, 87.1 ± 3.8, 86.9 ± 3.8, 87.7 ± 3.3, and 87.6 ± 2.8, respectively. There was no significant difference in AOFAS scores, Bohler's angle, Gissane's angle, calcaneal length, and height between the two groups (P > 0.05). The good to excellent rate of the PR group (80.8%) was less than that of the STA group (91.7%) (P = 0.055). For Sanders III fractures, the good to excellent rate of the PR group (33.3%) was less than that of the STA group (76.9%) (P = 0.029). For calcaneal width recovery, the STA group performed better than the PR group (P < 0.05). The incidence of postoperative complications in the PR group (12.8%) was lower than that in the STA group (27.8%) (P = 0.026), of which the incidence of wound complications was 3.8% in the PR group and 13.9% in the STA group (P = 0.041). In addition, there was no significant difference in other postoperative complications such as sural nerve injury, peroneus longus and brevis muscle injury, calcaneal valgus symptoms, lateral impingement symptoms, and subtalar arthritis (P > 0.05). CONCLUSION: From the 8-10-year follow-up results of PR and STA as surgical procedures for the treatment of DIACF, it was found that there was no significant difference in the overall efficacy between them. STA was found to be superior to the PR in terms of the recovery of calcaneal width, providing more stable fixation for Sanders III fractures. PR was found to be more effective in reducing wound complications.

19.
Clin Cancer Res ; 26(6): 1460-1473, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31857432

RESUMO

PURPOSE: Therapies directed to specific molecular targets are still unmet for patients with triple-negative breast cancer (TNBC). Deubiquitinases (DUB) are emerging drug targets. The identification of highly active DUBs in TNBC may lead to novel therapies. EXPERIMENTAL DESIGN: Using DUB activity probes, we profiled global DUB activities in 52 breast cancer cell lines and 52 patients' tumor tissues. To validate our findings in vivo, we employed both zebrafish and murine breast cancer xenograft models. Cellular and molecular mechanisms were elucidated using in vivo and in vitro biochemical methods. A specific inhibitor was synthesized, and its biochemical and biological functions were assessed in a range of assays. Finally, we used patient sera samples to investigate clinical correlations. RESULTS: Two DUB activity profiling approaches identified UCHL1 as being highly active in TNBC cell lines and aggressive tumors. Functionally, UCHL1 promoted metastasis in zebrafish and murine breast cancer xenograft models. Mechanistically, UCHL1 facilitates TGFß signaling-induced metastasis by protecting TGFß type I receptor and SMAD2 from ubiquitination. We found that these responses are potently suppressed by the specific UCHL1 inhibitor, 6RK73. Furthermore, UCHL1 levels were significantly increased in sera of patients with TNBC, and highly enriched in sera exosomes as well as TNBC cell-conditioned media. UCHL1-enriched exosomes stimulated breast cancer migration and extravasation, suggesting that UCHL1 may act in a paracrine manner to promote tumor progression. CONCLUSIONS: Our DUB activity profiling identified UCHL1 as a candidate oncoprotein that promotes TGFß-induced breast cancer metastasis and may provide a potential target for TNBC treatment.

20.
EMBO Rep ; 21(1): e47030, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31858693

RESUMO

Comment on "USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7" by Kit Leng Lui et al.

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