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1.
Cancer Med ; 13(18): e70256, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39358989

RESUMEN

PURPOSE: To compare the efficacy of first-line regimens based on programmed cell death (or ligand) [PD-(L)1] blockade in extensive-stage small-cell lung cancer (ES-SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing chemo-immunotherapy (CIT) and chemotherapy (CT) in ES-SCLC patients stratified by LM. Overall survival (OS) and progression-free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Seven RCTs involving 3658 ES-SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti-PD-1 + CT (HR, 0.67; 95% CI, 0.54%-0.82%; p < 0.001) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84; 95% CI, 0.71%-0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti-PD-1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti-angiogenesis + anti-PD-L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. CONCLUSIONS: CIT is effective for ES-SCLC patients regardless of LM status. For patients with LM, PD-1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti-angiogenesis, PD-L1 blockade, and CT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas , Neoplasias Pulmonares , Metaanálisis en Red , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estadificación de Neoplasias , Supervivencia sin Progresión
2.
Eur J Med Chem ; 279: 116827, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39288596

RESUMEN

Anaplastic lymphoma kinase (ALK) fusion genes promote a variety of human malignancies. Although several ALK inhibitors have significantly improved disease prognosis in patients with ALK positive cancers, the persistent emergence of acquired drug-resistant mutations remain the major problem in clinic treatment. Adoption of new therapeutic strategies such as proteolysis targeting chimera (PROTAC) to overcome drug resistance in BTK/AR-related cancers have shown promising prospect. Herein, we reported the integrate ALK PROTACs through overall optimization of linker, revealed that subtle structural differences can lead to significant activity difference, indicating the key role of conformation of PROTACs in inducing the formation of E3-PROTAC-target protein ternary complexes. A series of rigid ALK PROTACs were developed through conjugation of Ceritinib and thalidomide, orally bioavailable PROTAC 4B (F = 14.22 %) was obtained by overall optimization of molecular properties. 4B effectively induced long lasting degradation of ALK fusion proteins and strong repression of downstream pathway in Karpas 299 cells (DC50 = 119.33 nM, Dmax = 97.1 %) and showed comparable anti-proliferative activity to Ceritinib (IC50 = 3.11 ± 0.08 nM vs IC50 = 1.31 ± 0.43 nM). Furthermore, 4B significantly inhibited the growth of Karpas 299 xenografts in vivo with TGI of 49.5 % and showed superior anti-proliferative activity against G1202R mutation to Ceritinib (IC50 = 52.82 nM vs IC50 = 109.5 nM). Overall, 4B is expected to be a potential treatment for ALK-driven malignancies.

3.
Transl Lung Cancer Res ; 13(8): 1841-1850, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39263041

RESUMEN

Background: The risk and risk factors of extrathoracic metastasis at initial diagnosis in T≤3cmN0 lung cancer patients are not fully understood. We aimed to develop a model to predict the risk of extrathoracic metastasis in those patients. Methods: Clinicopathological data of patients were collected from Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable analyses using logistic regression were conducted to identify risk factors. A predictive model and corresponding nomogram were developed based on the risk factors. The model was assessed using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, and decision curve. Results: A total of 20,057 T≤3cmN0 patients were enrolled, of whom 251 (1.25%) were diagnosed with extrathoracic metastasis at the initial diagnosis. Aged ≤50 [odds ratio (OR): 2.05, 95% confidence interval (CI): 1.19-3.53, P=0.01] and aged ≥81 [1.65 (1.05-2.58), P=0.03], Hispanic [1.81 (1.20-2.71), P=0.004], location of bronchus [3.18 (1.08-9.35), P=0.04], larger tumor size, pleural invasion, and a history of colorectal cancer [2.01 (1.01-4.00), P=0.046] were independent risk factors. In the training cohort and validation cohort, the AUCs of the developed model were 0.727, 0.728 respectively, and the results of Hosmer-Lemeshow test were P=0.47, P=0.61 respectively. The decision curve showed good clinical meaning of the model. Conclusions: Extrathoracic metastasis at initial diagnosis in T≤3cmN0 lung cancer patients was not rare. The model based on the risk factors showed good performance in predicting the risk of extrathoracic metastasis.

4.
Transl Lung Cancer Res ; 13(7): 1530-1543, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39118884

RESUMEN

Background: Mediastinal station 8 lymph node dissection (8LND) is recommended by guidelines but not routinely performed in real world clinical practice. This study aimed to investigate the effect of 8LND on the prognosis of pT≤3 cmN0M0 lung adenocarcinoma. Methods: Patients undergoing lobectomy were retrospectively enrolled from West China Hospital from 2011 to 2019. Kaplan-Meier method and log-rank test were used to investigate the effects of 8LND on the progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). Propensity score matching (PSM) was used to reduce the confounding effects. Multivariable analysis was conducted to evaluate the effect of 8LND in the matched patients. Subgroup analyses were conducted to further identify patients who might benefit from 8LND. Results: A total of 1,209 patients were enrolled and 261 (21.59%) patients underwent 8LND. Before PSM, for patients who received 8LND (8LND+ patients) and who did not (8LND- patients), the 5-year PFS was 91.34%, 88.03% (P=0.03) respectively, the 5-year OS was 97.10%, 92.78% (P=0.03) respectively, and the 5-year CSS was 97.67%, 93.59% (P=0.05) respectively. After PSM, 8LND+ patients still had better PFS (P=0.006), OS (P=0.01), and CSS (P=0.03) as compared to 8LND- patients. Multivariable analyses showed that 8LND was associated with lower risk of disease progression [hazard ratio (HR): 0.46; 95% confidence interval (CI): 0.26-0.80; P=0.007], and lower risk of death (HR: 0.33; 95% CI: 0.13-0.85; P=0.02). The survival benefit of 8LND was still found in subgroup analyses in male patients, smokers, patients with a pT2 tumor (≤3 cm), and patients with a poorly differentiated tumor. Conclusions: 8LND could improve the survival of T≤3 cmN0M0 lung adenocarcinoma patients. Routine 8LND is recommended, especially in male, smokers, patients with a pT2 tumor (≤3 cm), and patients with a poorly differentiated tumor.

5.
J Alzheimers Dis ; 101(2): 589-601, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39213059

RESUMEN

Background: A range of imaging modalities have reported Alzheimer's disease-related abnormalities in individuals experiencing subjective cognitive decline (SCD). However, there has been no consistent local abnormality identified across multiple neuroimaging modalities for SCD. Objective: We aimed to investigate the convergent local alterations in amyloid-ß (Aß) deposition, glucose metabolism, and resting-state functional MRI (RS-fMRI) metrics in SCD. Methods: Fifty SCD patients (66.4±5.7 years old, 19 men [38%]) and 15 normal controls (NC) (66.3±4.4 years old, 5 men [33.3%]) were scanned with both [18F]-florbetapir PET and [18F]-fluorodeoxyglucose PET, as well as simultaneous RS-fMRI from February 2018 to November 2018. Voxel-wise metrics were retrospectively analyzed, including Aß deposition, glucose metabolism, amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality(DC). Results: The SCD group showed increased Aß deposition and glucose metabolism (p < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (p < 0.05, uncorrected) in the left dorsal precuneus (dPCu). Furthermore, the dPCu illustrated negative resting-state functional connectivity with the default mode network. Regarding global Aß deposition positivity, the Aß deposition in the left dPCu showed a gradient change, i.e., Aß positive SCD > Aß negative SCD > Aß negative NC. Additionally, both Aß positive SCD and Aß negative SCD showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu. Conclusions: The dorsal precuneus, an area implicated in early AD, shows convergent neuroimaging alterations in SCD, and might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory.


Asunto(s)
Disfunción Cognitiva , Imagen por Resonancia Magnética , Imagen Multimodal , Lóbulo Parietal , Tomografía de Emisión de Positrones , Humanos , Masculino , Disfunción Cognitiva/diagnóstico por imagen , Femenino , Anciano , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/metabolismo , Persona de Mediana Edad , Péptidos beta-Amiloides/metabolismo , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Glucosa/metabolismo
6.
Cell Biochem Biophys ; 82(3): 2957-2975, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39014186

RESUMEN

Podocyte damage plays a crucial role in the occurrence and development of diabetic nephropathy (DN). Accumulating evidence suggests that dysregulation of transcription factors plays a crucial role in podocyte damage in DN. However, the biological functions and underlying mechanisms of most transcription factors in hyperglycemia-induced podocytes damage remain largely unknown. Through integrated analysis of data mining, bioinformatics, and RT-qPCR validation, we identified a critical transcription factor forkhead box F1 (FOXF1) implicated in DN progression. Moreover, we discovered that FOXF1 was extensively down-regulated in renal tissue and serum from DN patients as well as in high glucose (HG)-induced podocyte damage. Meanwhile, our findings showed that FOXF1 might be a viable diagnostic marker for DN patients. Functional experiments demonstrated that overexpression of FOXF1 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and fibrosis in HG-induced podocytes damage. Mechanistically, we found that the downregulation of FOXF1 in HG-induced podocyte damage was caused by DNMT1 directly binding to FOXF1 promoter and mediating DNA hypermethylation to block FOXF1 transcriptional activity. Furthermore, we found that FOXF1 inhibited the transcriptional expression of miR-342-3p by binding to the promoter of miR-342, resulting in reduced sponge adsorption of miR-342-3p to E2F1, promoting the expression of E2F1, and thereby inhibiting HG-induced podocytes damage. In conclusion, our findings showed that blocking the FOXF1/miR-342-3p/E2F1 axis greatly alleviated HG-induced podocyte damage, which provided a fresh perspective on the pathogenesis and therapeutic strategies for DN patients.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1 , Nefropatías Diabéticas , Regulación hacia Abajo , Factor de Transcripción E2F1 , Factores de Transcripción Forkhead , Glucosa , MicroARNs , Podocitos , Podocitos/metabolismo , Podocitos/patología , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Humanos , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/genética , Glucosa/farmacología , Glucosa/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Animales , Apoptosis/efectos de los fármacos , Metilación de ADN , Regiones Promotoras Genéticas , Ratones , Proliferación Celular
7.
Chem Biodivers ; : e202401210, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007531

RESUMEN

Four novel Mesona chinensis Benth polysaccharides were isolated using aqueous alcohol precipitation. Their molecular weights were determined using high-performance gel permeation chromatography: MA1 (2.3 kDa), MA2 (80.5 kDa), MA3 (180.9 kDa), and MA4 (635.2 kDa), and their compositions were analyzed using GC-MS. The polysaccharides were mainly D-glucose, D-galactose, L-Rhamnose, D-arabinose, D-xylose, and D-mannose. The structural characteristics were further analyzed using infrared spectrophotometry and were identified as a type of pyrrhic sugar. An insulin-induced insulin resistance model of HepG2 cells and oleic acid-induced fat accumulation model of insulin were established to evaluate the hypolipidemic effects. Three Bacteroides spp. [Bacteroides thetaiotaomicron (BT), B. ovatus (BO), and B. cellulosilyticus (BC)] that were negatively correlated with lipid-lowering activity were used to evaluate the lipid-lowering activity of polysaccharides. The Bacteroides metabolites of MA1 and MA2 exhibited hypolipidemic effects and antioxidant activities and could potentially be used as lipid-lowering supplements.

8.
Langmuir ; 40(27): 13834-13843, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38920318

RESUMEN

The chiral nematic phase structure, formed by the self-assembly of cellulose nanocrystals (CNCs) in an aqueous suspension and maintained in a solid film, shows great potential for optical applications. To achieve complex structures in optical devices, it is crucial to subject CNCs to specific shearing processes, such as spinning and printing. Understanding the structural and property changes of the CNC liquid crystal phase in these processes is of utmost importance. In this study, we investigated the effect of adding tannic acid (TA) on the rheological properties and cholesteric phase structures of CNCs/TA mixed suspensions. By calculating the surface site interaction points, we observed that TA can adsorb onto the surface of CNC rods in suspensions through hydrogen bonding. Through characterization techniques, such as polarized optical microscopy, rheology, and synchrotron SAXS, we examined the effects of TA addition on the microstructure and rheological properties of the CNC liquid crystal phase and clarified the change relating to the system composition. Under the same CNC concentration, the volume fraction of the anisotropic phase, the pitch, and the rod spacing of the cholesteric phase were not significantly affected by the addition of TA. However, the system viscosity was significantly reduced with the appropriate amount of TA (2 wt %), in a wide range of CNC concentrations (up to 15 wt % CNCs). The flow indexes (n) in Region I and Region III of steady-state shear curves of CNCs/TA systems (11-15 wt % CNCs) were compared. Moreover, we introduced the well-established theoretical models for liquid crystal polymers to tentatively interpret Region I of the CNCs/TA cholesteric phase and realized that increased numbers of smaller cholesteric-phase domains in the CNCs/TA system and interfacial modification by TA may contribute to the fluidity change. The feature of the domain texture of CNCs/TA systems is verified by polarized optical microscopy observations.

9.
BMC Surg ; 24(1): 147, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734595

RESUMEN

BACKGROUND: Surgical interventions are more effective than nonsurgical approaches in providing a cure for stress urinary incontinence (SUI). In this study, we aimed to assess the benefits of tension-free vaginal tape (TVT) abbrevo by comparing its efficacy and complications to those of TVT obturator. METHODS AND RESULTS: 49 and 47 patients at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between January 2013 and December 2016 were included in the TVT-O and TVT-A groups, respectively. We evaluate the success rate and perioperative complications associated with TVT-O and TVT-A. A questionnaire that utilized the Patient Global Impression of Improvement (PGI-I) Scale was employed to assess the impact of surgery. Patients were followed up at 1 year, and 5 years after surgery. There were no statistically significant differences found in the efficacy of the TVT-A group and TVT-O group during both the one-year (p = 0.4) and five-year (p = 0.32) follow-up periods. In the period of one-year follow-up, 95.9% (n = 47) of patients in the TVT-O group and 95.8% (n = 45) of patients in the TVT-A group demonstrated improvement. During the period of five-year follow-up, 87.8% (n = 43) of patients in the TVT-O group and 93.6% (n = 44) of patients in the TVT-A group demonstrated improvement. CONCLUSIONS: Based on our findings, TVT-A and TVT-O procedures exhibited similarly high success rates and low frequencies of complications.


Asunto(s)
Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo , Humanos , Incontinencia Urinaria de Esfuerzo/cirugía , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Estudios de Seguimiento , Anciano , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos Quirúrgicos Urológicos/instrumentación
10.
Lung Cancer ; 191: 107799, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38669725

RESUMEN

OBJECTIVES: The aim of this study was to investigate the clinical benefit and necessity of neoadjuvant programmed cell death (or ligand) (PD-(L)1) blockades in resectable non-small cell lung cancer (NSCLC) patients with negative PD-L1 expression. MATERIALS AND METHODS: Randomized control trials (RCTs) that compared event-free survival (EFS), overall survival (OS), major pathological response (MPR), and/or pathological complete response (pCR) between neoadjuvant chemo-immunotherapy (nCIT) and neoadjuvant chemotherapy (nCT) for patients with resectable NSCLC stratified by PD-L1 expression were eligible for inclusion in the study. Data regarding the pathological response and EFS were evaluated by the odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random and fixed models. RESULTS: A total of six RCTs involving 3,194 patients with resectable NSCLC with or without neoadjuvant immunotherapy were included. Compared with nCT alone, nCIT significantly improved pCR (18.3 % vs. 3.0 %; OR, 5.64; 95 % CI, 3.22-9.89; P < 0.001), MPR (38.9 % vs. 15.5 %; OR, 3.57; 95 % CI, 2.10-6.05; P < 0.001), and EFS (HR, 0.75; 95 % CI, 0.62-0.90; P = 0.002) in PD-L1 <1 % NSCLC patients. In addition, PD-L1 ≥1 % was associated with higher rates of pCR (32.8 % vs. 18.3 %; OR, 2.28; 95 % CI, 1.40-3.73; P = 0.001) and MPR (53.9 % vs. 38.9 %; OR, 1.84; 95 % CI, 1.22-2.79; P = 004) and longer EFS (HR, 0.44 vs. 0.75) in the setting of nCIT compared with PD-L1 <1 %. nCIT improved only OS in NSCLC patients with PD-L1 ≥1 % but not in patients with PD-L1 <1 %. CONCLUSIONS: The use of nCIT should be recommended for resectable NSCLC patients with negative PD-L1 expression, as nCIT significantly improved the pathological response and EFS in these patients. The benefit to PD-L1-negative patients treated with nCIT on OS remains to be validated.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Terapia Neoadyuvante , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Terapia Neoadyuvante/métodos , Antígeno B7-H1/metabolismo , Inmunoterapia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de Puntos de Control Inmunológico/uso terapéutico
11.
Med Sci Monit ; 30: e942324, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38494662

RESUMEN

BACKGROUND Infection and chronic rejection remain major issues for kidney transplant recipients (KTRs). The present study aimed to explore the association of CD4+/CD8+ T cell ratio (CD4+/CD8+) and platelet/lymphocyte ratio (PLR) with long-term infection and chronic renal insufficiency in KTRs. MATERIAL AND METHODS KTRs admitted to a single hospital from June 2014 to December 2021 were divided into infected (164) and non-infected (107) groups based on clinical data. The levels of CD4+/CD8+, PLR, neutrophil/lymphocyte ratio (NLR), and C-reactive Protein (CRP) in KTRs with long-term infection, and their correlation with chronic kidney insufficiency, were analyzed. Survival analysis was used to evaluate the risk factors for long-term infection and chronic kidney insufficiency. RESULTS Spearman correlation analysis showed that chronic kidney insufficiency was positively correlated with PLR, and negatively correlated with CRP and CD4+/CD8+ (P<0.05). PLR was positively correlated with CRP, procalcitonin, erythrocyte sedimentation rate, and NLR, but negatively with CD4+/CD8+. CD4+/CD8+ was correlated with CRP, NLR, and PLR (P<0.05). Survival analysis and survival curves showed that PLR and CD4+/CD8+ were risk factors for long-term infection and chronic kidney insufficiency in KTRs (P<0.05). CONCLUSIONS CD4+/CD8+ and PLR were associated with long-term complications, and were risk factors for long-term infection and chronic kidney insufficiency in KTRs.


Asunto(s)
Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Trasplante de Riñón/efectos adversos , Recuento de Plaquetas , Estudios Retrospectivos , Subgrupos de Linfocitos T/metabolismo , Proteína C-Reactiva/metabolismo
12.
J Hand Surg Asian Pac Vol ; 29(2): 96-103, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38494167

RESUMEN

Background: Various studies have examined occlusive dressings in fingertip amputations and reported good outcomes. Occlusive dressing preserves appropriate pH, cell accumulation and moisture for healing, thereby limiting scar formation and deformity. To our knowledge, no study was performed in tropical Asia. This study aims to demonstrate the viability of healing fingertip amputations through secondary intention using an effective dressing technique, even in warm tropical climates. Methods: All patients who presented to our institution with fingertip amputations from 1 July 2020 to 31 July 2022 were analysed retrospectively. Seventeen patients (15 male, 2 female) of mean age 37.2 ± 9.4 years old with 18 injured digits were retrospectively analysed. Twelve (66.7%) were Allen Type III injuries, and one patient required distal phalangeal K-wire fixation. During the patient's final review, static 2-point discrimination, pulp sensation, fingertip contour and nail deformities alongside the last measured range of motion (ROM) of the injured finger was recorded. Treatment duration and days of leave taken were also summed and assessed. Results: Patients were dressed with semi-occlusive dressing for an average of 20.1 ± 6.83 days. The average total duration of dressing is 36.78 ± 18.88 days over an average of 7.18 ± 4.03 dressing visits. Mean duration of follow-up was 108 ± 63.46 days. Good outcome measures in sensation, pulp contour, nail deformity and ROM similar to existing literature were reported. Conclusions: Occlusive dressing remains a viable and feasible treatment option for fingertip amputation even in a tropical climate. While this simple treatment method may require more effort from patient, wound healing was attained after 36.8 ± 18.9 days of dressing. Level of Evidence: Level IV (Therapeutic).


Asunto(s)
Traumatismos de los Dedos , Enfermedades de la Uña , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Clima Tropical , Estudios Retrospectivos , Intención , Traumatismos de los Dedos/cirugía , Cicatrización de Heridas
13.
Nat Prod Res ; : 1-6, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38226496

RESUMEN

Two new sesquiterpene glycosides, 8α,12,15ß-trihydroxycopacamphan-15-O-ß-D-glucopyranoside (1) and dendrobiumane C-11-O-ß-D-glucopyranoside (2), along with three known terpenoids (3-5) were isolated from the aerial stems of Dendrobium henanense. Their structures were elucidated based on NMR-spectroscopic and HR-MS analyses. All compounds could reduce the levels of NO, TNF-α and IL-1ß in LPS-induced RAW264.7 cells with IC50 values ranging from 10.37 to 34.55 µΜ.

15.
Cell Rep ; 42(10): 113205, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37792530

RESUMEN

Target of Rapamycin Complex 1 (TORC1) is a conserved eukaryotic protein complex that links the presence of nutrients with cell growth. In Saccharomyces cerevisiae, TORC1 activity is positively regulated by the presence of amino acids and glucose in the medium. However, the mechanisms underlying nutrient-induced TORC1 activation remain poorly understood. By utilizing an in vivo TORC1 activation assay, we demonstrate that differential metabolism of glucose activates TORC1 through three distinct pathways in yeast. The first "canonical Rag guanosine triphosphatase (GTPase)-dependent pathway" requires conversion of glucose to fructose 1,6-bisphosphate, which activates TORC1 via the Rag GTPase heterodimer Gtr1GTP-Gtr2GDP. The second "non-canonical Rag GTPase-dependent pathway" requires conversion of glucose to glucose 6-phosphate, which activates TORC1 via a process that involves Gtr1GTP-Gtr2GTP and mitochondrial function. The third "Rag GTPase-independent pathway" requires complete glycolysis and vacuolar ATPase reassembly for TORC1 activation. We have established a roadmap to deconstruct the link between glucose metabolism and TORC1 activation.


Asunto(s)
Proteínas de Unión al GTP Monoméricas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Glucosa/metabolismo , Guanosina Trifosfato/metabolismo
17.
Front Pharmacol ; 14: 1189058, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37711169

RESUMEN

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696.

18.
Front Endocrinol (Lausanne) ; 14: 1124143, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37576970

RESUMEN

Background: SOX17 has been identified as a critical factor in specification of human primordial germ cells, but whether SOX17 regulates development of germ cells after sex differentiation is poorly understood. Methods: We collected specimens of gonadal ridge from an embryo (n=1), and ovaries of foetuses (n=23) and adults (n=3). Germ cells were labelled with SOX17, VASA (classic germ cells marker), phosphohistone H3 (PHH3, mitosis marker) and synaptonemal complex protein 3 (SCP3, meiosis marker). Results: SOX17 was detected in both cytoplasm and nucleus of oogonia and oocytes of primordial and primary follicles from 15 to 28 gestational weeks (GW). However, it was exclusively expressed in cytoplasm of oogonia at 7 GW, and in nucleus of oocytes in secondary follicles. Co-expression rates of SOX17 in VASA+ germ cells ranged from 81.29% to 97.81% in foetuses. Co-staining rates of SOX17 and PHH3 or SCP3 were 0%-34% and 0%-57%, respectively. Interestingly, we distinguished a subpopulation of SOX17+VASA- germ cells in fetal ovaries. These cells clustered in the cortex and could be co-stained with the mitosis marker PHH3 but not the meiosis marker SCP3. Conclusions: The dynamic expression of SOX17 was detected in human female germ cells. We discovered a population of SOX17+ VASA- germ cells clustering at the cortex of ovaries. We could not find a relationship between mitosis or meiosis and SOX17 or VASA staining in germ cells. Our findings provide insight into the potential role of SOX17 involving germ cells maturation after specification, although the mechanism is unclear and needs further investigation.


Asunto(s)
Células Germinativas , Ovario , Humanos , Femenino , Adulto , Ovario/metabolismo , Oocitos , Oogonios/metabolismo , Feto , Factores de Transcripción SOXF/genética , Factores de Transcripción SOXF/metabolismo
19.
Arthrosc Tech ; 12(7): e1161-e1169, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37533927

RESUMEN

Various surgical techniques exist to repair or reconstruct complete scapholunate (SL) interosseous ligament tears, including capsulodesis, static or dynamic tenodesis, ligament reconstruction with tendon graft, bone-retinaculum-bone reconstruction, and the reduction and association of the scaphoid and lunate (RASL) procedure. The choice of surgical technique depends on arthroscopic assessment using the Geissler classification and European Wrist Arthroscopy Society staging of SL injury. This article describes arthroscopy-assisted extracapsular SL reconstruction using free tendon graft and internal brace augmentation for the treatment of unrepairable complete SL interosseous ligament tears.

20.
Sci Rep ; 13(1): 11372, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452108

RESUMEN

Farmers' participation in food safety governance is an important part of food safety social co-governance, and the accurate identification of its influencing factors and their related paths is of guiding significance to the scientific decision-making of food safety governance. The system of influencing factors of farmers' participation in food safety governance was constructed from four dimensions, and the influence network of each dimension was revealed by decision laboratory analysis (DEMATEL). The hierarchical structure and correlation path of influencing factors were determined by interpretive structural model (ISM), and the attributes of influencing factors were further classified by cross influence matrix multiplication (MICMAC). The results show that the influencing factors of farmers' participation in food safety governance can be divided into seven levels, among which the level of education and the status of village cadres are the fundamental characteristic factors. The degree of rural informatization, the intensity of government supervision, the promotion of village committees, the response of the government and the degree of disclosure of government information are the deep core factors, and risk cognition, political trust and family eating habits are special factors. Taking the importance and attribute status of farmers' participation in food safety governance into decision-making considerations is of great significance to improve the efficiency of food safety governance.


Asunto(s)
Agricultura , Agricultores , Humanos , Agricultura/métodos , Confianza , Inocuidad de los Alimentos , Cognición , China
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