Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 214
Filtrar
1.
Cell Prolif ; : e13702, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956970

RESUMEN

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

2.
Clin Neurol Neurosurg ; 244: 108454, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39047392

RESUMEN

OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL). METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher's exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (ß2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40 g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (ß2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40 g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Anciano , Adulto , Adulto Joven , Anciano de 80 o más Años , Pronóstico , Adolescente , Microglobulina beta-2/sangre , Invasividad Neoplásica
3.
Heliyon ; 10(11): e32429, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38933983

RESUMEN

The relation between aphids and Sclerotinia stem rot (SSR) in oilseed rape is rarely examined because they are often studied alone. We have observed a significant correlation between the number of aphids and the occurrence of SSR in our field studies. Electropenetrography (EPG) was used to evaluate the effects of Brevicoryne brassicae (Linnaeus) on two oilseed rape cultivars while acquiring, vectoring and inoculating of Sclerotinia sclerotiorum Lib. (de Bary) ascospores. The results demonstrated that aphid feeding followed by the application of an ascospore suspension significantly increased S. sclerotiorum incidence. Aphids were capable of adhering to ascospores and carrying them to healthy plants, thereby causing diseases. The results of the EPG analysis indicated that aphid feeding behaviour was significantly altered in all leaf tissue levels following infection with S. sclerotiorum. Aphids initiated their first puncture significantly sooner than the control group, began probing mesophyll cells earlier, significantly increased the frequency of both short probes and intracellular punctures and had a significantly shorter pathway duration. On infected aphid-susceptible cultivars, aphids secreted more saliva but had reduced ingestion compared with aphids feeding on non-infected oilseed rape. In addition, ascospores can affect aphid feeding behaviour by adhering to aphids. Aphids carrying ascospores punctured cells earlier, with a significant increase in the frequency and duration of short probes and cell punctures, shortened pathway durations, increased salivation and reduced ingestion compared with aphids not carrying ascospores. On aphid-susceptible cultivars, aphids carrying ascospores delayed puncture onset, but on resistant cultivars, puncture onset was shortened. There is a correlation between aphids and S. sclerotiorum. The impact of S. sclerotiorum on aphid feeding behaviour is directional, favouring the spread of the fungus. This promotion does not appear to be altered by the aphid resistance of the cultivar.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 469-475, 2024 May 15.
Artículo en Chino | MEDLINE | ID: mdl-38802906

RESUMEN

OBJECTIVES: To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS: A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS: The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS: The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Masculino , Femenino , Niño , Preescolar , Pronóstico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Adolescente , Lactante , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad
5.
J Med Chem ; 67(11): 8730-8756, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38817193

RESUMEN

The secretory glutaminyl cyclase (sQC) and Golgi-resident glutaminyl cyclase (gQC) are responsible for N-terminal protein pyroglutamation and associated with various human diseases. Although several sQC/gQC inhibitors have been reported, only one inhibitor, PQ912, is currently undergoing clinic trials for the treatment of Alzheimer's disease. We report an X-ray crystal structure of sQC complexed with PQ912, revealing that the benzimidazole makes "anchor" interactions with the active site zinc ion and catalytic triad. Structure-guided design and optimization led to a series of new benzimidazole derivatives exhibiting nanomolar inhibition for both sQC and gQC. In a MPTP-induced Parkinson's disease (PD) mouse model, BI-43 manifested efficacy in mitigating locomotor deficits through reversing dopaminergic neuronal loss, reducing microglia, and decreasing levels of the sQC/gQC substrates, α-synuclein, and CCL2. This study not only offers structural basis and new leads for drug discovery targeting sQC/gQC but also provides evidence supporting sQC/gQC as potential targets for PD treatment.


Asunto(s)
Aminoaciltransferasas , Bencimidazoles , Inhibidores Enzimáticos , Animales , Aminoaciltransferasas/antagonistas & inhibidores , Aminoaciltransferasas/metabolismo , Bencimidazoles/química , Bencimidazoles/farmacología , Bencimidazoles/síntesis química , Cristalografía por Rayos X , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/uso terapéutico , Relación Estructura-Actividad , Modelos Animales de Enfermedad , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Humanos , Ratones Endogámicos C57BL , Descubrimiento de Drogas , Masculino , Modelos Moleculares
6.
J Fungi (Basel) ; 10(3)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38535210

RESUMEN

Aphids and Sclerotinia stem rot in oilseed rape are often studied in isolation, and their relationship is rarely explored. Our field studies have revealed a significant positive correlation between the number of aphids and the incidence of Sclerotinia stem rot. Hence, starting with the colonizing stages of the two pests, Breveroryne brassicae was assessed for its potential to acquire, transmit, and inoculate Sclerotinia sclerotiorum by being sprayed with an ascospore suspension. Moreover, distinctions in aphid feeding behavior were examined between aphids on inoculated/uninoculated winter and spring oilseed rape plants or aphids, both with and without S. sclerotiorum ascospores, using electropenetrography (EPG). The results showed that aphid feeding followed by dropping ascospore suspension significantly increased the incidence of S. sclerotiorum. Ascospores were able to adhere to aphids and were carried by aphids to healthy plants, causing disease. The results of the EPG analysis indicated that aphid feeding behavior was significantly altered in all leaf tissue levels following infection with S. sclerotiorum. Specifically, aphids initiated their first puncture significantly sooner, began probing mesophyll cells earlier, had a significantly shorter pathway duration, and secreted saliva more frequently but reduced salivation prior to feeding and ingestion compared to aphids feeding on uninfected oilseed rape. Additionally, the feeding behavior of aphids carrying ascospores was markedly different from that of aphids not carrying ascospores, implying that ascospores directly influence aphid feeding behavior but that this influence appeared to be beneficial only for S. sclerotiorum infection. Aphids carrying ascospores started to puncture cells more quickly, with a significant increase in the frequency and duration of short probes and cell punctures, shortened pathway durations, and reduced salivation before feeding compared to aphids not carrying ascospores. It is clear that there is an interaction between aphids and S. sclerotiorum. The impact of S. sclerotiorum on aphid feeding behavior is directional, favoring the spread of the fungus.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38530766

RESUMEN

BACKGROUND AND OBJECTIVES: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety. METHODS: We used a quasi-experimental design and selected 2 adult wards with similar properties as the experimental and comparison groups by convenience sampling. Data collection was from December 1, 2021, to June 30, 2022, at a teaching hospital in central Taiwan. Team members of the ward performing huddles formed the experimental group, and they participated 2 times per week in 15-minute huddles from 8:15 to 8:30 am for a total of 4 weeks. The comparison group adopted the routine team care process. Both groups completed the Safety Attitudes Questionnaire during the pre- and post-tests of the study. RESULTS: The experimental group scored significantly higher in the post-test than in the pre-test in all aspects of safety attitudes, with the exception of stress recognition. These improved aspects were teamwork climate (76.47 ± 15.90 vs 83.29 ± 13.52, P < .001), safety climate (75.94 ± 16.14 vs 82.81 ± 13.74, P < .001), job satisfaction (74.34 ± 20.22 vs 84.40 ± 17.22, P <.001), perceptions of management (78.02 ± 19.99 vs 85.51 ± 15.97, P < .001), and working conditions (78.85 ± 17.87 vs 86.81 ± 14.74, P < .001). CONCLUSION: Through the huddles, clinical team members improved their understanding of different aspects of safety attitudes. Such a study provided ward units with real-time improvement and adjustment in terms of patient safety during their medical work processes with better patient safety.

9.
Diabetol Metab Syndr ; 16(1): 40, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341600

RESUMEN

BACKGROUND: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. METHODS: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. RESULTS: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. CONCLUSIONS: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

10.
J Multidiscip Healthc ; 16: 3599-3607, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38024136

RESUMEN

Objective: A huddle is a short, regular meetings to discuss existing or emerging patient safety issues. Hospital administrators can encourage healthcare staff to voluntarily examine the potential occurrence and severity of risks, thereby enhancing awareness of patient safety. The purpose of this study is to explore the effects of huddle intervention on patient safety culture among medical team members and related factors. Methods: We used a one-group pretest-posttest research design and convenience sampled 109 members of the general internal medicine ward team members from a medical center in central Taiwan. They participated 2 times per week in 15-min huddles from 08:15 to 08:30 in the morning, which lasted for a total of 4 weeks. The process was based on submitted ideas, approved ideas, research ideas and standardization, and data on the safety attitudes questionnaire (SAQ) were collected during the huddles' intervention pretest and posttest. Results: After the huddle intervention, we found significantly improved scores for safety attitude, teamwork climate (76.49±16.13 vs 83.26±13.39, p < 0.001), safety climate (75.07±16.07 vs 82.63±13.72, p < 0.001), job satisfaction (73.67±19.84 vs 83.39±17.21, p < 0.001), perceptions of management (77.87±19.99 vs 84.86±16.03, p < 0.001) and working conditions (78.96±18.16 vs 86.18±14.90, p < 0.001). Correlation analyses on the differences between pretest and posttest showed that age had a significant correlation with safety climate (r = 0.22, p = 0.022) and working conditions (r = 0.20, p = 0.035). The number of times to participate in a huddle had a significant correlation with teamwork climate (r = 0.33, p =<.001), safety climate (r = 0.30, p = 0.002), job satisfaction (r = 0.19, p = 0.043), and work conditions (r = 0.28, p = 0.003). Conclusion: Huddles improve clinical team members' understanding of different dimensions and relate factors of safety attitudes. Implementation of the huddles involved standardized process will help hospital administrators understand the steps to parallel expansion to other wards.

11.
Plants (Basel) ; 12(10)2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37653889

RESUMEN

Plant viruses improve transmission efficiency by directly and indirectly influencing vector behavior, but the impact of plant cultivars on these modifications is rarely studied. Using electropenetrography (EPG) technology, a comparative study of the effects of turnip mosaic virus (TuMV) infection on quantitative probing behaviors of the cabbage aphid (Brevicoryne brassicae) was conducted on two oilseed rape cultivars ('Deleyou6' and 'Zhongshuang11'). Compared to mock-inoculated plants, cabbage aphids on infected plants increased the frequency of brief probing, cell penetration, and salivation. Additionally, aphids on infected 'Deleyou6' prolonged cell penetration time and decreased ingestion, but not on infected 'Zhongshuang11', suggesting that aphids were more likely to acquire and vector TuMV on the aphid-susceptible cultivar 'Deleyou6' than on resistant cultivars. TuMV also affected aphid probing behavior directly. Viruliferous aphids reduced the pathway duration, secreted more saliva, and ingested less sap than non-viruliferous aphids. In comparison with non-viruliferous aphids, viruliferous aphids started the first probe earlier and increased brief probing and cell penetration frequencies on the aphid-resistant cultivar 'Zhongshuang11'. Based on these observations, viruliferous aphids can be inoculated with TuMV more efficiently on 'Zhongshuang11' than on 'Deleyou6'. Although aphid resistance and TuMV infection may influence aphid probing behavior, oilseed rape resistance to aphids does not impede TuMV transmission effectively.

12.
World Neurosurg ; 179: e387-e396, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37652134

RESUMEN

OBJECTIVE: Relapse of the central nervous system (CNS) is a rare but fatal complication in diffuse large B-cell lymphoma (DLBCL). The purpose of this study is to learn how to identify high-risk patients and take effective preventive measures. METHODS: We retrospectively analyzed 1,290 adult patients with DLBCL at Peking University Cancer Hospital and Shanxi Bethune Hospital between 2010 and 2020. RESULTS: There were 55 patients with CNS relapse who had a median follow-up of 5 years. The risk of CNS relapse was 1.58% in the low-risk group, 5.66% in the moderate-risk group, and 11.67% in the high-risk group based on CNS International Prognostic Index (CNS-IPI). We found that CNS-IPI and testicular involvement were risk factors for CNS relapse, with OR 1.913 (95% CI: 1.036∼3.531; P = 0.038) versus. OR 3.526 (95% CI: 1.335∼9.313; P = 0.011), respectively. Intrathecal MTX and/or cytarabine prophylaxis was used in 166 patients (13.94%), intravenous (IV) high-dose methotrexate (HD-MTX) prophylaxis in 8 patients (0.67%), and intrathecal plus intravenous prophylaxis in 15 patients (1.26%). There was no significant difference in CNS relapse risk between IT, HD-MTX, and no prophylaxis recipients (12.7% vs. 0% vs. 23.6%, respectively, P = 0.170). The risk of CNS relapse was similar whether or not patients accepted prophylaxis (5-year risk 4.1% vs. 2.2%, P = 0.140). CONCLUSIONS: Central nervous system (CNS) relapse is associated with high risk CNS-IPI and testicular involvement. Therefore, it is necessary to pursue novel prophylactic strategies for CNS relapse.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Adulto , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Neoplasias del Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Metotrexato/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema Nervioso Central , Rituximab , Ciclofosfamida
13.
Heliyon ; 9(7): e17591, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37483803

RESUMEN

Objective: To observe the effect of renal artery denervation (RDN) on cardiac function in patients with acute myocardial infarction after percutaneous coronary intervention (AMI-PCI). Methods: This is a single-centre, prospective randomized controlled study. A total of 108 AMI-PCI patients were randomly assigned to the RDN group or the control group at 1:1 ratio. All patients received standardized drug therapy after PCI, and patients in the RDN group underwent additional RDN at 4 weeks after the PCI. The follow-up period was 6 months after RDN. Echocardiography-derived parameters, cardiopulmonary exercise testing (CPET) data, Holter electrocardiogram, heart rate variability (HRV) at baseline and at the 6 months-follow up were analyzed. Results: Baseline indexes were similar between the two groups (all P > 0.05). After 6 months of follow-up, the echocardiography-derived left ventricular ejection fraction was significantly higher in the RDN group than those in the control group. Cardiopulmonary exercise test indicators VO2Max, metabolic equivalents were significantly higher in the RDN group than in the control group. HRV analysis showed that standard deviation of the normal-to-normal R-R intervals, levels of square root of the mean squared difference of successive RR intervals were significantly higher in the RDN group than those in the control group. Conclusions: RDN intervention after PCI in AMI patients is associated with improved cardiac function, improved exercise tolerance in AMI patients post PCI. The underlying mechanism of RDN induced beneficial effects may be related to the inhibition of sympathetic nerve activity and restoration of the sympathetic-vagal balance in these patients.

15.
Phytomedicine ; 117: 154903, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37301185

RESUMEN

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Factor 2 Relacionado con NF-E2 , Transformación Celular Neoplásica
16.
Orthop Surg ; 15(7): 1893-1903, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37259903

RESUMEN

OBJECTIVE: Obtaining sufficient decompression and solid fusion and avoiding approach-related injuries simultaneously are still challenging for the treatment of hard disc herniation in thoracolumbar junction. A combined full-endoscopic decompression and interbody fusion via a transforaminal approach was used to achieve this goal. The purpose of this study was to introduce the technical notes and clinical outcomes of this novel technique. METHODS: Twenty segments of hard disc herniations in the thoracolumbar junction of 14 patients treated with full-endoscopic interbody fusion via the transforaminal approach between January 2018 and September 2021 were analyzed. The patients were an average age of 43.3 years. Full-endoscopic interbody fusion and discectomy via the transforaminal approach were performed under local anesthesia, followed by percutaneous pedicle screw system fixation under general anesthesia. Imaging, including magnetic resonance imaging (MRI), computed tomography (CT), and X-ray, was carried out. MRI was performed on the second day and 3 months postoperatively. CT was performed on the second day, 6 months, and 1 year (as needed) postoperatively. Back and radicular pain, neurological function, and thoracic spine function were scored using a visual analog scale, the Nurick scale, and modified Japanese Orthopaedic Association (mJOA) scale, and the Oswestry disability index at 1 week, 3 months, 6 months, and 1 year postoperatively. RESULTS: All the operations were successfully completed, and no intraoperative conversion of the surgical methods occurred. Postoperative thoracolumbar junction MRI and CT examinations of all the patients revealed a sufficiently decompressed spinal cord or cauda equina, without any residual compression. At the 1-year follow-up, all the surgical segments were fused. Back and radicular pain was relieved in all the patients, and neurological function was restored. The average recovery rate of the mJOA was 72.5%, including seven excellent, five good, and two fair cases. Although dural tears occurred in two cases during the operation, no cerebrospinal fluid leakage or pseudomeningocele occurred during follow-up. No other surgical complications were noted. CONCLUSIONS: A combined full-endoscopic decompression and interbody fusion via a transforaminal approach can achieve complete spinal canal decompression and solid interbody fusion with fewer approach-related injuries. It is a safe and effective minimally invasive spine surgery for treating hard disc herniation in the thoracolumbar junction.


Asunto(s)
Desplazamiento del Disco Intervertebral , Fusión Vertebral , Humanos , Adulto , Desplazamiento del Disco Intervertebral/cirugía , Descompresión Quirúrgica/métodos , Resultado del Tratamiento , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Dolor , Estudios Retrospectivos
17.
Front Oncol ; 13: 1083776, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36937397

RESUMEN

Objective: Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database. Methods: SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method. Results: A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS. Conclusion: Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.

18.
Int J Endocrinol ; 2023: 8080578, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36704419

RESUMEN

Background: Currently, both metabolic syndrome and hyperuricaemia have attracted extensive attention in public health. The correlation between uric acid and metabolic syndrome is controversial. Research on the relationship between uric acid and metabolic syndrome in community-dwelling elderly people is relatively lacking. The purpose of this study is to explore the relationship between uric acid and metabolic syndrome in the community-dwelling elderly people. Design: Cross-sectional study. Methods: We collected the physical examination data of 1,267 elderly people in Gutian community in Wuhan and used SPSS IBM 25.0 for data analysis. Correlation and logistic regression analyses were performed, and ROC curves were drawn. Results: The uric acid level of the nonmetabolic syndrome group was lower than that of the metabolic syndrome group (337.31 vs. 381.91 µmol/L; P < 0.05). Uric acid was positively correlated with systolic blood pressure (r = 0.177, P < 0.001), diastolic blood pressure (r = 0.135, P < 0.001), body mass index (r = 0.234, P < 0.001), waist circumference (r = 0.283, P < 0.001), and triglycerides (r = 0.217, P < 0.05). High-density lipoprotein cholesterol (r = -0.268, P < 0.001) showed the opposite trend. Logistic regression analysis results suggested that uric acid is a risk factor for metabolic syndrome. The result is described as exp (B) and 95% CI (1.003 [1.001, 1.005]). Based on the receiver operating characteristic curve, we found that the area under the curve of uric acid to diagnose metabolic syndrome was 0.64 (sensitivity: 79.3%, specificity: 45.1%). Conclusion: We observed an association between uric acid levels and metabolic syndrome in the elderly Chinese population. The best threshold value for uric acid in predicting metabolic syndrome diagnosis was 314.5 µmol/l.

19.
World Neurosurg ; 169: e235-e244, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36334710

RESUMEN

OBJECTIVE: To evaluate and describe the clinical efficacy and safety of a modified unilateral biportal endoscopic lumbar discectomy. METHODS: From February 2019 to February 2020, patients who met the inclusion criteria were treated using a modified unilateral biportal endoscopic lumbar discectomy. During the operation, the herniated disc was removed and the ligamentum flavum was preserved. Clinical efficacy was assessed via postoperative imaging and follow-up. RESULTS: A total of 70 patients were followed up for more than 2 years, including 51 males and 19 females, aged 49.4 ± 16.0 years. All operations were completed and no complications were noted. Postoperative lumbar magnetic resonance imaging showed that the decompression of the nerve root was sufficient and the ligamentum flavum was preserved in all patients. Postoperative lumbar CT showed that the caudal lamina and inferior articular process of the cephalad vertebral were partially removed. Lower back and leg pain were significantly relieved after surgery, and the Oswestry Disability Index was significantly improved compared to presurgery measurements (P < 0.01). After 2 years of follow-up, the sensory and muscle strength of nerve roots were significantly recovered (P < 0.01). According to the MacNab score of the patients, 40 cases were defined as "excellent," 26 cases were "good," 2 cases were "fair," and 2 cases were "poor." CONCLUSIONS: Modified unilateral biportal endoscopic lumbar discectomy can completely remove a lumbar herniated disc; relieve lower back and leg pain; improve lumbar function; reduce the risk of dural tearing, cerebrospinal fluid leakage, and epidural hematoma; and reduce the epidural adhesion and arachnoiditis caused by ligamentum flavum resection.


Asunto(s)
Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Masculino , Femenino , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Endoscopía/métodos , Discectomía/métodos , Resultado del Tratamiento , Dolor/cirugía , Región Lumbosacra/cirugía , Estudios Retrospectivos , Discectomía Percutánea/métodos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA