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1.
Anticancer Drugs ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39079172

RESUMEN

The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro, it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC.

2.
Orthop Surg ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39077885

RESUMEN

OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.

3.
Cancer Nurs ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38941110

RESUMEN

BACKGROUND: Interventions to foster resilience may promote mental health recovery after exposure to stressors. However, comprehensive systematic syntheses of such evidence in family members of pediatric cancer patients are lacking. OBJECTIVE: To systematically review and meta-analyze the evidence for the effects of psychological interventions at fostering resilience in family members of pediatric cancer patients. METHODS: PubMed, Cumulative Index to Nursing and Allied Health Literature, and 9 other databases were searched for articles published until March 2023. Empirical studies on psychological interventions to improve resilience in family members of pediatric cancer patients were included. Full-text and quality appraisals were performed independently by 2 reviewers. Pooled effect sizes were calculated using random-effects meta-analyses. RESULTS: Seventeen studies were included, of which 10 were included in the meta-analyses. There was a positive effect of interventions on resilience at postintervention time points, but no effects on depressive symptoms, stress, or well-being. The improvement in resilience was sustained in the short term (≤3 months) and medium term (>3 to ≤6 months), with delayed effects on depressive symptoms and stress. In the 6 studies that reported moderate effect sizes, the interventions comprised problem-solving skills, cognitive strategies, promotion of personal strength, and social resources. CONCLUSION: The findings indicated that psychological interventions targeting resilience have the potential to positively affect the resilience and mental health outcomes of family members, particularly parents. IMPLICATIONS FOR PRACTICE: Psychological interventions targeting resilience hold promise in improving the mental health of family members. Future interventions should clearly specify the characteristics of the intervention, such as mode of delivery, format, and duration.

4.
Phytomedicine ; 128: 155526, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38564921

RESUMEN

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.


Asunto(s)
Alcaloides , Aterosclerosis , Macrófagos , Morus , Animales , Humanos , Masculino , Ratones , Alcaloides/farmacología , Antiinflamatorios/farmacología , Aterosclerosis/tratamiento farmacológico , Dieta Alta en Grasa , Células Endoteliales/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Morus/química , Células RAW 264.7
5.
J Thorac Oncol ; 19(6): 883-897, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38311022

RESUMEN

INTRODUCTION: Household particulate matter (PM) air pollution is substantially associated with lung cancer. Nevertheless, the global burden of lung cancer attributable to household PM2.5 is still uncertain. METHODS: In this study, data from the Global Burden and Disease Study 2019 are used to thoroughly assess the burden of lung cancer associated with household PM2.5. RESULTS: The number of deaths and disability-adjusted life-years (DALYs) attributable to household PM2.5 was found to be 0.08 million and 1.94 million, respectively in 2019. Nevertheless, the burden of lung cancer attributable to household PM2.5 decreased from 1990 to 2019. At the sociodemographic index (SDI) district level, the middle SDI region had the most number of lung cancer deaths and DALYs attributable to household PM2.5. Moreover, the burden of lung cancer was mainly distributed in low-SDI regions, such as Sub-Saharan Africa. Conversely, in high-SDI regions, the age-standardized mortality rate and age-standardized DALY rate of lung cancer attributable to household PM2.5 exhibit the most rapid declines. The burden of lung cancer attributable to household PM2.5 is heavier for men than for women. The sex difference is more obvious in the elderly. CONCLUSIONS: The prevalence of lung cancer attributable to household PM2.5 has exhibited a declining trend from 1990 to 2019 owing to a concurrent decline in household PM2.5 exposure.


Asunto(s)
Carga Global de Enfermedades , Neoplasias Pulmonares , Material Particulado , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Material Particulado/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Contaminación del Aire/efectos adversos , Salud Global/estadística & datos numéricos , Adulto , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/estadística & datos numéricos
6.
J Viral Hepat ; 30(10): 793-802, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37533208

RESUMEN

Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.


Asunto(s)
Carcinoma Hepatocelular , Hígado Graso , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hígado Graso/patología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Fibrosis , Asia/epidemiología , Virus de la Hepatitis B
7.
Endocr J ; 70(10): 959-967, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37468264

RESUMEN

An association exists between nonalcoholic fatty liver disease (NAFLD) and growth hormone (GH). Patients with growth hormone deficiency (GHD) may be more susceptible to NAFLD. The prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) in GHD patients is currently unknown. Multiple databases were searched for experiments related to NAFLD (or NASH) and GHD. Screening, quality evaluation and data extraction were carried out independently by two authors. Analyses used random or fixed effects models, including NAFLD prevalence, NASH prevalence, odds ratio (OR) and 95% confidence interval (CI). We included 10 studies with a total of 782 participants. The results showed that the prevalence of NAFLD in GHD patients was 51% (95% CI: 39-63). The risk of NAFLD in GHD patients was significantly higher than that in controls (age-, sex- or body mass index-matched, without GHD) (pooled OR = 4.27, 95% CI: 1.33-13.68%, p = 0.015). The prevalence of NASH in GHD patients was 18% (95% CI: 5-31). The prevalence of NAFLD in GHD patients is significantly higher than that in the general population, especially NASH. There is a need to develop targeted strategies for the early identification, prevention, or control of NAFLD/NASH in patients with GHD.


Asunto(s)
Hipopituitarismo , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Hipopituitarismo/complicaciones , Medición de Riesgo , Hormona del Crecimiento , Hígado
8.
Anal Methods ; 15(27): 3346-3352, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37401339

RESUMEN

Bromochloroacetamide (BCAcAm) is the main haloacetamide (HAcAm) detected in drinking water in different regions and exhibits strong cytotoxicity and genotoxicity. However, there is no appropriate method for detecting BCAcAm in urine or other biological samples, and thus, the internal exposure level in the population cannot be accurately assessed. In this study, a gas chromatography-electron capture detector (GC-ECD) was combined with salting-out assisted dispersive liquid-liquid microextraction (SA-DLLME) to develop a rapid and robust method for BCAcAm detection in urine of mice continuously exposed to BCAcAm. The factors influencing the pre-treatment procedure, including the type and volume of extraction and disperser solvents, extraction and standing time, and the amount of salt, were evaluated systematically. Under the optimised conditions, the analyte achieved good linearity in the spiked concentration range of 1.00-400.00 µg L-1, and the correlation coefficient was higher than 0.999. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.17 µg L-1 and 0.50 µg L-1, respectively. The recoveries ranged from 84.20% to 92.17%. The detection of BCAcAm at three different calibration levels using this method afforded an intra-day precision of 1.95-4.29%, while the inter-day precision range was 5.54-9.82% (n = 6). This method has been successfully applied to monitor the concentration of BCAcAm in mouse urine in toxicity experiments and can provide technical support for assessing human internal exposure levels and health risks in later studies.


Asunto(s)
Microextracción en Fase Líquida , Humanos , Ratones , Animales , Microextracción en Fase Líquida/métodos , Solventes/química , Cromatografía de Gases/métodos , Límite de Detección , Cloruro de Sodio
9.
Chemosphere ; 335: 139085, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37263514

RESUMEN

Chlorination is widely used to disinfect drinking water to keep humans safe from microorganisms. During chlorination, chlorine and its compounds react with contaminants to form disinfection by-products (DBPs). Toxicological and epidemiological studies have demonstrated that trihalomethanes (THMs) are the most widely investigated DBPs in drinking water, and their exposure has been associated with some adverse health effects. However, studies about risk characteristics in this field are limited. We estimated the health risks of THMs exposure in drinking water through multi-pathways, and systematically analyzed the factors influencing health risks of THMs in Wuxi, China. A total of 488 drinking water samples were collected and analyzed for THMs from four water treatment utilities from 2008 to 2016 in Wuxi. And water exposure parameters were obtained from 602 participants by structured questionnaires. The median concentration of THMs ranged from 6.71 µg/L to 9.18 µg/L. The cumulative cancer risk of THMs exposure through multi-pathways was 1.26 × 10-4, and CHBr2Cl made the largest contribution to the total cancer risk (48.25%). The non-cancer risk of THMs exposure was 2.02 × 10-1. Health risks of the exposure to THMs in drinking water in summer were significantly higher than that in winter (P = 0.0003 for cancer risk, and P = 5.95 × 10-7 for non-cancer risk). In our study, the average individual disability-adjusted life years (DALYs) lost was 1.27 × 10-4 per person-year (ppy). This study attempted to use DALYs for risk assessment of THMs, which will provide useful information for risk comparison and prioritization of hazards in drinking water. This suggested that potential higher risk might exist, and possible measures could be considered to decrease the health risks.


Asunto(s)
Desinfectantes , Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Trihalometanos/toxicidad , Trihalometanos/análisis , Desinfección , Cloruros , Medición de Riesgo , China , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Desinfectantes/análisis
10.
Expo Health ; : 1-14, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37360513

RESUMEN

Long-term atmospheric quality monitoring of fine particulate matter (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) was performed in Wuxi from 2016 to 2021. In total, 504 atmospheric PM2.5 samples were collected, and PM2.5-bound 16 PAHs were detected. The PM2.5 and ∑PAHs level decreased annually from 2016 to 2021, from 64.3 to 34.0 µg/m3 and 5.27 to 4.22 ng/m3, respectively. The benzo[a]pyrene (BaP) levels of 42% of the monitoring days in 2017 exceeded the recommended European Union (EU) health-based standard of 1 ng/m3. Five- and six-ring PAHs were found, including benz[a]anthracene, benzo[k]fluoranthene (Bkf), BaP, and benzo[g,h,i]perylene, which were the dominant components (indicating a prominent petroleum, biomass, and coal combustion contribution) using molecular diagnostic ratios and positive matrix factorization analysis. Moreover, PM2.5 and PAHs were significantly negatively associated with local precipitation over a period of six years. Statistically significant temporal and spatial distribution differences of PM2.5, and ∑PAHs were also found. The toxicity equivalent quotient (TEQ) of total PAHs was 0.70, and the TEQ of BaP (0.178) was the highest, followed by that of Bkf (0.090), dibenz[a,h]anthracene (Dah) (0.048), and indeno[1,2,3-cd]pyrene (0.034). The medians of the incremental lifetime cancer risk for long-term exposure to PAHs were 2.74E-8, 1.98E-8, and 1.71E-7 for children, teenagers, and adults, respectively, indicating that the carcinogenic risk of PAHs pollution in air was acceptable to local residents in this area. Sensitivity analysis revealed that BaP, Bkf, and Dah significantly contributed to carcinogenic toxicity. This research provides comprehensive statistics on the local air persistent organic pollutants profile, helps to identify the principal pollution source and compounds, and contributes to the prevention of regional air pollution. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-023-00572-x.

11.
Orthop Surg ; 15(6): 1694-1701, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37073103

RESUMEN

BACKGROUND: Intradural disc herniation(IDH) caused by trauma is a rare type of disease,which is difficult to diagnose clinically and is easily misdiagnosed. We received a patient with the disease, reported the case to share the process of diagnosis and treatment and put forward our own opinions, so as to increase the probability of correct diagnosis. CASE PRESENTATION: We report the case of a 48-year-old male who fell from a scaffold at a height of 2 m. Later, he developed low back pain, restricted movement, numbness and hyperalgesia of the lower left limb, and decreased left muscle strength. He was diagnosed with IDH. Treatment with posterior decompression and intramedullary decompression with pedicle screw internal fixation was performed. His postoperative course was uneventful, and he underwent regular follow up for 1 year. Good neurologic symptom improvement was achieved. CONCLUSIONS: IDH is rare, and comprehensive consideration and film reading can improve the correct diagnosis rate. Accurate diagnosis and early decompression of laminae and intramedullary decompression can lead to good recovery after neurologic impingement.


Asunto(s)
Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar , Fusión Vertebral , Masculino , Humanos , Persona de Mediana Edad , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/complicaciones , Vértebras Lumbares/cirugía , Fusión Vertebral/efectos adversos , Dolor de la Región Lumbar/etiología
12.
Photodiagnosis Photodyn Ther ; 42: 103544, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37004836

RESUMEN

Gallbladder cancer (GBC) is a rare but frequently fatal biliary tract malignancy that is typically discovered when it is already advanced. In this study, we investigated a novel technique for the quick and non-invasive diagnosis of GBC based on serum surface-enhanced Raman spectroscopy (SERS). SERS spectra of serum from 41 patients with GBC and 72 normal subjects were recorded. Principal component analysis-linear discriminant analysis (PCA-LDA), and PCA-support vector machine (PCA-SVM), Linear SVM and Gaussian radial basis function-SVM (RBF-SVM) algorithms were used to establish the classification models, respectively. When the Linear SVM was used, the overall diagnostic accuracy for classifying the two groups could achieve 97.1%, and when RBF-SVM was used, the diagnostic sensitivity of GBC was 100%. The results demonstrated that SERS combination with a machine learning algorithm is a promising candidate to be one of the diagnostic tools for GBC in the future.


Asunto(s)
Neoplasias de la Vesícula Biliar , Fotoquimioterapia , Humanos , Espectrometría Raman/métodos , Neoplasias de la Vesícula Biliar/diagnóstico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Algoritmos , Análisis de Componente Principal
13.
Orthop Surg ; 15(5): 1241-1248, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36915232

RESUMEN

OBJECTIVE: Although the role of anterior cervical titanium plate system in stabilizing the spine sequence and promoting bone graft fusion has been widely recognized, more and more attention has been paid to the design of the plate itself and the complications caused by it. In order to solve the problems of poor stability of internal fixation, plate displacement and screw looseness, we designed the new PRUNUS spine plate system. Hence, the present study was conducted to describe observe and evaluate the clinical efficacy of a new type of three-leaf reinforced cervical anterior screw plate system (PRUNUS nailing system) developed for anterior cervical surgery. METHODS: A retrospective analysis of 56 patients from June 2018 to October 2019 was used. Twenty-seven patients with cervical spine disease treated with new PRUNUS nail plate internal fixation were selected as the observation group, and 29 patients with cervical spine disease treated with conventional cervical anterior screw fixation were selected as the control group. Postoperative follow-up was performed. Cervical stability, internal fixation position and bone graft fusion were evaluated according to imaging data. The operative time, intraoperative blood loss, cervical Cobb angle, pain visual analogue scale (VAS), and Japanese orthopaedic association (JOA) were compared between the two groups. Spinal function scores and neurological improvement rates were used to evaluate the clinical efficacy of the new PRUNUS spine plate. RESULTS: The patients were followed up for 5-18 months, with an average of 7.33 months. The average operative time of the observation group was 98.4 ± 9.2 min, and the mean intraoperative blood loss was 65.3 ± 10.6 ml, which were significant different from the control group's 109.7 ± 9.4 minutes (P < 0.05), 72.9 ± 15.6 ml (P < 0.05). Comparison between the two groups in postoperative and final follow-up of cervical Cobb angle, JOA score and improvement rate, VAS score and preoperative comparison showed no significant differences (P > 0.05). CONCLUSION: The new PRUNUS spine plate system can be applied to the anterior cervical spine surgery, and its clinical efficacy was similar to the traditional cervical anterior plate. But PRUNUS simplified the operation process, especially suitable for the surgical treatment of anterior cervical revision and osteoporosis patients.


Asunto(s)
Vértebras Cervicales , Fusión Vertebral , Humanos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Fusión Vertebral/métodos , Resultado del Tratamiento
14.
Talanta ; 259: 124457, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36989965

RESUMEN

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. GBC is difficult to diagnose and treat at an early stage because of the lack of effective serum markers and typical symptoms, resulting in low survival rates. This study aimed to investigate the applicability of dried serum Fourier-transform infrared (FTIR) spectroscopy combined with machine learning algorithms to correctly differentiate patients with GBC from patients with gallbladder disease (GBD), cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC) and healthy individuals. The differentiation between healthy individuals and GBC serum was better using principal component analysis (PCA) and linear discriminant analysis (LDA) for six spectral regions, especially in the protein (1710-1475 cm-1) and combined (1710-1475 + 1354-980 cm-1) region. However, the PCA-LDA model poorly differentiated GBC from GBD, CCA, and HCC in serum spectra. We evaluated the PCA- LDA, PCA-support vector machine (SVM), and radial basis kernel function support vector machine (RBF-SVM) models for GBC diagnosis and found that the RBF-SVM model performed the best, with 88.24-95% accuracy, 95.83% sensitivity, and 78.38-94.44% specificity in the 1710-1475 + 1354-980 cm-1 region. This study demonstrated that serum FTIR spectroscopy combined with the RBF-SVM algorithm has great clinical potential for GBC screening.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Humanos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Neoplasias de la Vesícula Biliar/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Aprendizaje Automático , Biomarcadores , Máquina de Vectores de Soporte
15.
Pharmacol Res ; 184: 106464, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36162600

RESUMEN

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.


Asunto(s)
Melanoma , Proteínas Nucleares , Animales , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/genética , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas B-raf/genética , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neoplasias de la Úvea
16.
Orthop Surg ; 13(7): 2000-2007, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34523793

RESUMEN

OBJECTIVE: To analyze correlations between the selection of microtitanium plates with different specifications for use in a cervical vertebral dome expansion laminoplasty. METHODS: Sixteen patients that underwent the cervical vertebral dome expansion laminoplasty with a cervical spinal stenosis angioplasty procedure for treatment of their cervical spinal cords were recruited at our hospital. From February 2017 to September 2018, medical records confirmed that all patients underwent cervical CT and MRI tests pre- and postsurgery. The anteroposterior diameter of the spinal canal, changes in the cross-sectional area of the spinal canal, and the pre- and postsurgery distance of the cervical spinal cord after applying microtitanium plates with different lengths were measured by Mimics version 17.0 software (Materialise NV, Leuven, Belgium). A statistical regression and correlation analysis of relevant specification parameters of the microtitanium plate was then studied. RESULTS: As the size of the microtitanium plate increased, we found that the cross-sectional area of cervical spinal canal and distance between the descendants of the lamina and the distance of cervical spinal cord concordantly increased, and these data changes linearly. The regression equation associated with sagittal diameter, cross-sectional area, and posterior movement distance of the cervical spinal cord was obtained. CONCLUSION: According to the correlation analysis of imaging data changes, the regression equation was obtained to guide the selection of microtitanium plates with appropriate specifications in a cervical vertebral dome expansion laminoplasty.


Asunto(s)
Placas Óseas , Vértebras Cervicales/cirugía , Diseño de Equipo , Laminoplastia/instrumentación , Estenosis Espinal/cirugía , Anciano , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estenosis Espinal/diagnóstico por imagen , Titanio , Tomografía Computarizada por Rayos X
17.
Orthop Surg ; 13(7): 1969-1978, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34523808

RESUMEN

OBJECTIVE: To evaluate the safety and stability of 3D-printed interbody fusion cages (3D-printed cages) in anterior cervical discectomy and fusion (ACDF) by investigating the mid- and long-term follow-up outcomes. METHODS: In this prospective study, the clinical data of 30 patients with CSM admitted to the Second Hospital of Shanxi Medical University from May 2012 to May 2014 were analyzed. The cohort comprised 18 males and 12 females with an average age of 60.22 ± 3.2 years. All patients were examined by X-ray, CT and MRI before the operation. A total of 30 cases of CSM were treated by ACDF with 3D printed cage implantation. Mid- and long-term follow-ups were performed after the surgery. Clinical efficacy was evaluated by comparing the JOA score, SF-36 score, change in neurological function, cervical curvature index (CCI), vertebral intervertebral height (VIH) and fusion rate before the operation, 6 months after the operation, and at the last follow-up. RESULTS: Two of the 30 patients were lost to follow-up. The remaining patients were followed up for 48-76 (65.23 ± 3.54) months. The patients recovered satisfactorily with a significant clinical effect. The JOA score increased meanfully and the improvement rate was 89.4% at the final follow-up. The SF-36 score increased significantly from pre- to postoperatively. The height of the intervertebral space at the last follow-up was not statistically significantly different from that at 6 months after surgery (P > 0.05), showing that the height of the intervertebral space did not change much and the severity of cage subsidence (CS) decreased. The CCI improved from pre- to postoperatively. The CCI did not change much from the 6-month follow-up to the last follow-up. and the cage rate (CR) was 100% at the 6-month and last follow-ups. No severe complications, such as spinal cord injury, esophageal fistula, cerebrospinal fluid leakage, cervical hematoma or wound infection, occurred in any of the patients. CONCLUSION: The clinical and radiological results show that the application of 3D-printed cages in ACDF can significantly relieve symptoms. Moreover, 3D-printed cages can restore the curvature of the cervical spine, effectively maintain the intervertebral height for a long time, and prevent complications related to postoperative subsidence.


Asunto(s)
Vértebras Cervicales/cirugía , Discectomía/métodos , Impresión Tridimensional , Enfermedades de la Médula Espinal/cirugía , Fusión Vertebral/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
18.
Orthop Surg ; 13(5): 1496-1504, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34056862

RESUMEN

PURPOSE: To provide imaging evidence of the feasibility and clinical efficacy of a new full lamina back shift spinal canal enlargement technique. METHODS: A retrospective analysis was conducted on 64 patients with multisegment cervical spondylotic myelopathy caused by cervical stenosis. Of these, 32 patients underwent the new full lamina back shift spinal canal enlargement technique (as observation group) and 32 patients underwent single open-door miniature titanium plate internal fixation (as control group). The computed tomography (CT) data of both groups were imported into Mimics 17.0 software to measure the median sagittal diameter and cross-sectional area of the spinal canal. Photoshop CS5 was employed to measure the drift distance of the spinal cord on MR images to perform a comparative study of the imaging parameters from the two groups. RESULTS: The T2-weighted MR images in both groups showed continuous recovery of the cerebrospinal fluid signal in the C3 -C7 range. The enlarged spinal canal cross-sectional area (mm2 ) of each segment after the new full lamina back shift spinal canal enlargement technique was 130.90 ± 20.52 (C3 ), 180.81 ± 18.86 (C4 ), 240.48 ± 35.43 (C5 ), 145.93 ± 36.94 (C6 ), and 153.16 ± 36.28 (C7 ), and the enlarged median sagittal diameter (mm) was 5.31 ± 1.13 (C3 ), 8.8 ± 1.28 (C4 ), 10.28 ± 1.68 (C5 ), 9.46 ± 1.48 (C6 ), and 9.22 ± 1.12 (C7 ). Both parameters were significantly superior to single open-door miniature titanium plate internal fixation (P < 0.05). No significant difference was detected in the drift distance of the spinal cord between the two groups (P > 0.05). CONCLUSION: The new full lamina back shift spinal canal enlargement technique achieved a thorough spinal canal decompression effect on imaging while ensuring a reasonable spinal drift distance and few surgical complications. The clinical curative effect of the new technique was precise.


Asunto(s)
Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Laminoplastia/métodos , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/cirugía , Fusión Vertebral/métodos , Anciano , Diagnóstico por Imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
19.
Virology ; 560: 76-85, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34051477

RESUMEN

Chronically SHIVSF162P3N-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4+ T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4+ T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Depleción Linfocítica , Virus de la Inmunodeficiencia de los Simios/inmunología , Viremia/sangre , Replicación Viral/inmunología , Animales , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , China , Citocinas/biosíntesis , Citocinas/sangre , Progresión de la Enfermedad , Femenino , Activación de Linfocitos/inmunología , Macaca fascicularis , Macrófagos/inmunología , Macrófagos/virología , Prueba de Estudio Conceptual , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Carga Viral
20.
Artículo en Inglés | MEDLINE | ID: mdl-32485650

RESUMEN

Drinking water disinfection may result in the formation of different classes of toxic disinfection by-products (DBPs). Haloacetamides (HAcAms) are an emerging class of nitrogenous DBPs (N-DBPs), which are generally more prevalent at lower concentrations in disinfected water than carbonaceous DBPs. Herein a fast, convenient, and effective method of analyzing 10 HAcAms in drinking water samples was demonstrated. This method was developed using gas chromatography /electron capture detection (GC/ECD) supplemented with automated solid phase extraction (auto-SPE). The variables for automated SPE procedures were further optimized, including the selection of SPE sorbents, types and volumes of extraction solvents, SPE washing solvents and wash times. Under optimized conditions, the instrumental linearity range was 0.5-150 µg L-1 with correlation coefficients>0.9975. The limits of detection and quantification of this method were 0.002-0.003 µg L-1 and 0.005-0.010 µg L-1, respectively. The recovery values ranged from 72.4% to 108.5%, and the relative standard deviations ranged from 3.3% to 9.1%. Therefore, the auto-SPE-GC-ECD method showed acceptable linearity and repeatability and was subsequently validated and applied to analyze 10 HAcAms in drinking water.


Asunto(s)
Acetamidas/análisis , Cromatografía de Gases/métodos , Agua Potable/química , Extracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/análisis , Acetamidas/química , Acetamidas/aislamiento & purificación , Desinfectantes/química , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación
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