Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 151
Filtrar
1.
BMC Musculoskelet Disord ; 25(1): 526, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982393

RESUMO

BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.


Assuntos
Acetábulo , Placas Ósseas , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas Ósseas , Titânio , Humanos , Acetábulo/cirurgia , Acetábulo/lesões , Fenômenos Biomecânicos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Adulto , Pessoa de Meia-Idade , Fraturas Ósseas/cirurgia , Fraturas Ósseas/fisiopatologia , Masculino , Feminino , Cadáver
2.
Carbohydr Res ; 541: 109167, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823063

RESUMO

This paper describes a mild and efficient catalytic deprotection method for isopropylidene ketals and benzylidene acetals using AcOH/H2O/DME(1,2-Dimethoxyethane). The method effectively removes ketal and acetal protecting groups from 2-deoxyglycosides which are prone to hydrolysis under acidic conditions. Moreover, it enables the selective removal of the terminal ketal over an internal one.


Assuntos
Glicosídeos , Glicosídeos/química , Glicosídeos/síntese química , Água/química , Estereoisomerismo , Cetonas/química , Catálise , Acetais/química , Estrutura Molecular
3.
Chem Commun (Camb) ; 60(57): 7359-7362, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38919041

RESUMO

This paper shows a novel oxidative functionalization of α-amino ketones to yield the corresponding α-ketoamides and α-acylimidates. The reaction proceeds via oxygen delivery from water/alcohols in conjunction with an electron acceptor and 4-dimethylaminopyridine (DMAP). Mechanistic study indicates that DMAP exhibits a dual function of nucleophilic catalysis and proton abstraction.

4.
Nat Prod Bioprospect ; 14(1): 29, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38740677

RESUMO

A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14-88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel-Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel-Crafts reactions.

5.
J Org Chem ; 89(7): 4851-4860, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38546258

RESUMO

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

6.
Heart Lung ; 65: 72-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432040

RESUMO

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.


Assuntos
Insuficiência Cardíaca , Albumina Sérica , Humanos , Prognóstico , Causas de Morte , Modelos de Riscos Proporcionais
7.
Gastric Cancer ; 26(6): 947-957, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37691031

RESUMO

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Metástase Linfática/patologia , RNA Longo não Codificante/genética , Transcriptoma , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfonodos/patologia
8.
J Org Chem ; 88(18): 13327-13330, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37615542

RESUMO

Salicylaldehyde works as an efficient photocatalyst for the intermolecular transalkylation of phthalimide. The well-designed dimethyl N-hydroxyphthalimide ester proves to be a good alkylation reagent. It inhibits the competing intramolecular alkylation of alkylating reagent, enabling the site-specific synthesis of N-substituted phthalimide.

9.
Org Lett ; 25(24): 4429-4433, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37294187

RESUMO

An iron-catalyzed direct aerobic α,ß-dehydrogenation of carbonyls has been reported. The combination of tert-butyl nitrite and N-hydroxyphthalimide worked as the organo cocatalyst system; thus, no extra transition metal reagents are required. A large variety of lactams and flavanones as well as lactone and thiochromen-4-one could be produced via this method in high yields.


Assuntos
Ferro , Elementos de Transição , Catálise , Lactamas
10.
J Environ Manage ; 340: 118009, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37105101

RESUMO

Canopies play an important role in nitrogen (N) redistribution in forest ecosystems, and ignoring the canopy's role might bias estimates of the ecological consequences of anthropogenic atmospheric N deposition. We investigated the effects of the approach of N addition (Canopy addition vs. Understory addition) and level of N addition (25 kg N ha-1yr-1 vs. 50 kg N ha-1yr-1) on microbial residual carbon (MRC) accumulation in topsoil and subsoil. We found that the response of MRC to both approach and level of N addition varied greatly with soil depth in a tropical forest over eight years of continuous N addition. Specifically, N addition enhanced the accumulation of fungal and total MRC and their contribution to soil organic C (SOC) pools in the topsoil, whereas it decreased the contribution of fungal and total MRC to SOC in the subsoil. The contrasting effects of N addition on MRC contribution at varying soil depths were associated with the distinct response of microbial residues production. Understory N addition showed overall greater effects on MRC accumulation than canopy N addition did. Our results suggest that the canopy plays an important role in buffering the impacts of anthropogenic atmospheric N deposition on soil C cycling in tropical forests. The depth-dependent response of microbial residues to N addition also highlights the urgent need for further studies of different response mechanisms at different soil depths.


Assuntos
Ecossistema , Nitrogênio , Nitrogênio/análise , Carbono , Florestas , Solo/química , Árvores
11.
Org Lett ; 25(16): 2863-2867, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37067379

RESUMO

CBZ6, a redox-neutral non-donor-acceptor-type organo-photocatalyst, presents a strong reductive potential with an oxidative potential of -2.16 V (vs SCE). It can work as a photosensitizer for both single-electron transfer and triplet energy transfer processes. This feature enables site-selective control in the intramolecular hydroarylation of acrylamides. Both 5-exo-trig and 6-endo-trig cyclization products could be prepared regiospecfically under mild conditions. No transition metal, halogen-containing reagents, or additional reductant or oxidant is involved. This process provides a concise and environmentally sustainable access to a series of oxindoles and dihydroquinolinones.

12.
Diabetol Metab Syndr ; 15(1): 37, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890514

RESUMO

OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice. METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed. RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella. CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

13.
Orthop Surg ; 15(2): 471-479, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36458444

RESUMO

OBJECTIVE: The percutaneous IS screws and the minimally invasive percutaneous plate are the most popular internal methods for Zone II unstable sacral fractures. However, the choice of fixation remains controversial for orthopaedic surgeons. The purpose of study was to evaluate and compare the clinical results of percutaneous iliosacral (IS) screw fixation under three-dimensional (3D) navigation and minimally invasive percutaneous plate fixation in the treatment of Zone II unstable sacral fractures. METHODS: A retrospective study was performed, including 64 patients with Zone II unstable sacral fractures who underwent percutaneous IS screw fixation under 3D navigation (navigation group) and minimally invasive percutaneous plate fixation (plate group) from January 2011 and March 2021 in our department. The age, gender, fracture type, mechanism of injury, injury severity score (ISS), time from admission to operation, operative time, intraoperative blood loss, hospital stay, incision length, follow-up time, time to clinical healing, and complications were recorded and analyzed. Matta standard was used to assess fracture reduction outcomes. The Majeed function system assessed functional outcomes at the last follow-up. RESULTS: The average follow-up time was (14.42 ± 1.57) months in the navigation group and (14.79 ± 1.37) months in the plate group. No statistical difference between the two groups in age, gender, fracture type, mechanism of injury, ISS, time from admission to operation, and time to clinical healing. However, significant differences were detected in operative time, intraoperative blood loss, hospital stay, and incision length (p < 0.001). According to Matta standard at 2 days postoperatively, the excellent and good rate was 91.42% in the navigation group, and it was 93.10% in the plate group. There was no significant difference between the two groups (p = 0.961). According to Majeed function system at the follow-up, the excellent and good rate was 97.14% in the navigation group, and 93.10% in the plate group. The difference between the two groups was not statistically significant (p = 0.748). There were no neurovascular injuries associated with this procedure. The incidence of complications was 44.82% (13/29) in the plate group, while 14.28% (5/35) in the navigation group (p = 0.007). CONCLUSION: This study found that compared with minimally invasive percutaneous plate fixation, percutaneous IS screw fixation under 3D navigation is a suitable option for the treatment of Zone II unstable sacral fractures. This approach is characterized by its shorter operation time, less surgical trauma, less bleeding, less hospital time, and fewer complications.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Fraturas da Coluna Vertebral , Humanos , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Ossos Pélvicos/cirurgia , Ossos Pélvicos/lesões , Resultado do Tratamento , Fraturas da Coluna Vertebral/cirurgia , Parafusos Ósseos
14.
J Back Musculoskelet Rehabil ; 36(2): 323-329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36155499

RESUMO

BACKGROUND: According to reports in the literature, osteoporotic vertebral compression fracture (OVCF) is associated with paraspinal muscle degeneration; however, the association between the severity of OVCF and paraspinal muscle degeneration is not clear. OBJECTIVE: The purpose of this study was to investigate the association between paraspinal muscle degeneration and OVCF severity in postmenopausal women. METHODS: Three hundred and seventy-six MRI images from 47 patients were collected and analyzed. Sagittal and axial coronal T2-weighted images were used to measure the fractured vertebra sagittal cross-sectional area (FSCSA), the adjacent normal vertebral body sagittal cross-sectional area (NSCSA), paraspinal muscle cross-sectional area (CSA), and the fat cross-sectional area (FCSA). The ratio of fractured vertebra compressed sagittal cross-sectional area (RCSA) and fatty infiltration ratio (FIR) was subsequently calculated. The formulas for RCSA and FIR calculations are as follows: RCSA = (NSCSA-FSCSA)/NSCSA; FIR = FCSA/CSA. RCSA and FIR represent the severity of OVCF and paraspinal muscle degeneration, respectively. RESULTS: The correlation between paraspinal muscle degeneration and OVCF severity was analyzed using the Pearson correlation, and multiple regression analysis was performed to explore related risk factors. OVCF severity was closely associated with paraspinal muscle degeneration (L3/4 FIR r= 0.704, P< 0.05; L4/5 FIR r= 0.578, P< 0.05; L5/S1 FIR r= 0.581, P< 0.05). Multiple regression analysis demonstrated that the risk factor for OVCF severity was L3/4 FIR (ß= 0.421, P= 0.033). CONCLUSION: OVCF severity was associated with the FIR of paraspinal muscles, and L3/4 FIR was a predictive factor for OVCF severity in postmenopausal women.


Assuntos
Fraturas por Compressão , Fraturas da Coluna Vertebral , Humanos , Feminino , Fraturas por Compressão/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Pós-Menopausa , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Atrofia Muscular , Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
15.
J Craniofac Surg ; 34(2): 680-683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36168119

RESUMO

Chronic hydrocephalus after clipping aneurysmal subarachnoid hemorrhage (aSAH) often results in poor outcomes. This study was to establish and validate model to predict chronic hydrocephalus after aSAH by least absolute shrinkage and selection operator logistic regression. The model was constructed from a retrospectively analyzed. Two hundred forty-eight patients of aSAH were analyzed retrospectively in our hospital from January 2019 to December 2021, and the patients were divided into chronic hydrocephalus (CH) group (n=55) and non-CH group (n=193) according to whether occurred CH within 3 months. In summary, 16 candidate risk factors related to chronic hydrocephalus after aSAH were analyzed. Univariate analysis was performed to judging the risk factors for CH. The least absolute shrinkage and selection operator regression was used to filter risk factors. Subsequently, the nomogram was designed by the above variables. And area under the curve and calibration chart were used to detect the discrimination and goodness of fit of the nomogram, respectively. Finally, decision curve analysis was constructed to assess the practicability of the risk of chronic hydrocephalus by calculating the net benefits. Univariate analysis showed that age (60 y or older), aneurysm location, modified Fisher grade, Hunt-Hess grade, and the method for cerebrospinal fluid drainage, intracranial infections, and decompressive craniectomy were significantly related to CH ( P <0.05). Whereas 5 variables [age (60 y or older), posterior aneurysm, modified Fisher grade, Hunt-Hess grade, decompression craniectomy] from 16 candidate factors were filtered by LASSO logistic regression for further research. Area under the curve of this model was 0.892 (95% confidence interval: 0.799-0.981), indicating a good discrimination ability. Meanwhile, the result of calibration indicated a good fitting between the prediction probability and the actual probability. Finally, decision curve analysis showed a good clinical efficacy. In summary, this model could conveniently predict the occurrence of chronic hydrocephalus after aSAH. Meanwhile, it could help physicians to develop personalized treatment and close follow-up for these patients.


Assuntos
Hidrocefalia , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/etiologia , Estudos Retrospectivos , Hidrocefalia/cirurgia , Aneurisma Intracraniano/cirurgia , Fatores de Risco
16.
Chem Commun (Camb) ; 58(84): 11871, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36218058

RESUMO

Correction for 'Efficiently increasing the radiative rate of TADF material with metal coordination' by Xian-Bao Cai et al., Chem. Commun., 2022, 58, 8970-8973, https://doi.org/10.1039/D2CC02930H.

17.
Ther Adv Chronic Dis ; 13: 20406223221117449, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003287

RESUMO

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.

18.
Chem Commun (Camb) ; 58(64): 8970-8973, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35861256

RESUMO

Herein, a simple and straightforward method to reduce dramatically the lifetime of a pure organic thermally activated delayed fluorescence (TADF) material VIA metal coordination is demonstrated. We designed a mononuclear silver complex [Ag(PPh2CH3)(TCzBN-PyPz)]BF4 (1) with a new emissive TCzBN-PyPz ligand. Even though the ligand and the metal complex have very similar emissive efficiencies and maximal peaks, over three orders of magnitude shorter lifetime of 0.59 µs for the complex than 2074 µs for ligand were obtained. Compared to other methods, the present protocol seems to be simple and highly effective.

19.
Ann Rheum Dis ; 81(4): 544-555, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34853001

RESUMO

OBJECTIVES: Dysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA. METHODS: Screening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes. RESULTS: Serial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin's regulations of chondrocytes. CONCLUSIONS: These findings not only provide new insights into the understanding of digoxin's chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.


Assuntos
Cartilagem Articular , Digoxina , Proteínas Relacionadas a Receptor de LDL , Osteoartrite , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Estudos de Coortes , Digoxina/farmacologia , Reposicionamento de Medicamentos , Humanos , Proteínas Relacionadas a Receptor de LDL/antagonistas & inibidores , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Ouabaína/farmacologia
20.
J Cancer Res Clin Oncol ; 148(11): 2959-2969, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34822015

RESUMO

OBJECTIVE: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC). METHODS: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups. RESULTS: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0-1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia. CONCLUSION: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT.


Assuntos
Leucopenia , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Cisplatino/efeitos adversos , Humanos , Quimioterapia de Indução/métodos , Leucopenia/induzido quimicamente , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...