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1.
Artigo em Inglês | MEDLINE | ID: mdl-38836956

RESUMO

PURPOSE: After robotic-assisted total knee arthroplasty (RA-TKA) surgery, some patients still experience joint discomfort. We aimed to establish an effective machine learning model that integrates radiomic features extracted from computed tomography (CT) scans and relevant clinical information to predict patient satisfaction three months postoperatively following RA-TKA. MATERIALS AND METHODS: After careful selection, data from 142 patients were randomly divided into a training set (n = 99) and a test set (n = 43), approximately in a 7:3 ratio. A total of 1329 radiomic features were extracted from the regions of interest delineated in CT scans. The features were standardized using normalization algorithms, and the least absolute shrinkage and selection operator regression model was employed to select radiomic features with ICC > 0.75 and P < 0.05, generating the Rad-score as feature markers. Univariate and multivariate logistic regression was then used to screen clinical information (age, body mass index, operation time, gender, surgical side, comorbidities, preoperative KSS score, preoperative range of motion (ROM), preoperative and postoperative HKA angle, preoperative and postoperative VAS score) as potential predictive factors. The satisfaction scale ≥ 20 indicates patient satisfaction. Finally, three prediction models were established, focusing on radiomic features, clinical features, and their fusion. Model performance was evaluated using Receiver Operating Characteristic curves and decision curve analysis. RESULTS: In the training set, the area under the curve (AUC) of the clinical model was 0.793 (95% CI 0.681-0.906), the radiomic model was 0.854 (95% CI 0.743-0.964), and the combined radiomic-clinical model was 0.899 (95% CI 0.804-0.995). In the test set, the AUC of the clinical model was 0.908 (95% CI 0.814-1.000), the radiomic model was 0.709 (95% CI 0.541-0.878), and the combined radiomic-clinical model was 0.928 (95% CI 0.842-1.000). The AUC of the radiomic-clinical model was significantly higher than the other two models. The decision curve analysis indicated its clinical application value. CONCLUSION: We developed a radiomic-based nomogram model using CT imaging to predict the satisfaction of RA-TKA patients at 3 months postoperatively. This model integrated clinical and radiomic features and demonstrated good predictive performance and excellent clinical application potential.

2.
J Orthop Surg Res ; 19(1): 259, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659060

RESUMO

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.


Assuntos
Teste de Materiais , Polietilenos , Escoliose , Humanos , Teste de Materiais/métodos , Fricção , Parafusos Ósseos , Técnicas In Vitro
3.
Virus Res ; 344: 199366, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38548137

RESUMO

Gamma-aminobutyric acid (GABA) signals in various non-neuronal cells including hepatocytes and some immune cells. Studies, including ours, show that type A GABA receptors (GABAARs)-mediated signaling occurs in macrophages regulating tissue-specific functions. Our recent study reveals that activation of GABAARs in liver macrophages promotes their M2-like polarization and increases HBV replication in mice. This short article briefly summarizes the GABA signaling system in macrophages and discusses potential mechanisms by which GABA signaling promotes HBV replication.


Assuntos
Hepatite B , Macrófagos , Receptores de GABA-A , Transdução de Sinais , Replicação Viral , Ácido gama-Aminobutírico , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Ácido gama-Aminobutírico/metabolismo , Hepatite B/virologia , Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/genética , Fígado/virologia , Fígado/metabolismo , Macrófagos/virologia , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética
4.
Environ Pollut ; 346: 123555, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38369090

RESUMO

Silver nanoparticles (AgNPs) are widely used in daily life and medical fields owing to their unique physicochemical properties. Daily exposure to AgNPs has become a great concern regarding their potential toxicity to human beings, especially to the central nervous system. Ferroptosis, a newly recognized programmed cell death, was recently reported to be associated with the neurodegenerative process. However, whether and how ferroptosis contributes to AgNPs-induced neurotoxicity remain unclear. In this study, we investigated the role of ferroptosis in neurotoxic effects induced by AgNPs using in vitro and in vivo models. Our results showed that AgNPs induced a notable dose-dependent cytotoxic effect on HT-22 cells and cognitive impairment in mice as indicated by a decline in learning and memory and brain tissue injuries. These findings were accompanied by iron overload caused by the disruption of the iron transport system and activation of NCOA4-mediated autophagic degradation of ferritin. The excessive free iron subsequently induced GSH depletion, loss of GPX and SOD activities, differential expression of Nrf2 signaling pathway elements, down-regulation of GPX4 protein and production of lipid peroxides, initiating ferroptosis cascades. The mitigating effects of ferrostatin-1 and deferoxamine on iron overload, redox imbalance, neuronal cell death, impairment of mice learning and memory, Aß deposition and synaptic plasticity reduction suggested ferroptosis as a potential molecular mechanism in AgNPs-induced neurotoxicity. Taken together, these results demonstrated that AgNPs induced neuronal cell death and cognitive impairment with Aß deposition and reduction of synaptic plasticity, which were mediated by ferroptosis caused by iron-mediated lipid peroxidation. Our study provides new insights into the underlying mechanisms of AgNPs-induced neurotoxicity and predicts potential preventive strategies.


Assuntos
Disfunção Cognitiva , Ferroptose , Sobrecarga de Ferro , Nanopartículas Metálicas , Camundongos , Humanos , Animais , Prata/toxicidade , Ferroptose/fisiologia , Nanopartículas Metálicas/toxicidade , Ferro/metabolismo , Disfunção Cognitiva/induzido quimicamente
5.
Spine J ; 24(6): 961-968, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38301900

RESUMO

BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the preplanned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.


Assuntos
Antibioticoprofilaxia , Cefuroxima , Fusão Vertebral , Infecção da Ferida Cirúrgica , Humanos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Masculino , Feminino , Antibioticoprofilaxia/métodos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Cefuroxima/administração & dosagem , Cefuroxima/uso terapêutico , Idoso , Estudos Retrospectivos , Antibacterianos/administração & dosagem , Adulto , Fatores de Tempo
6.
Mol Med ; 30(1): 27, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378457

RESUMO

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.


Assuntos
Reabsorção Óssea , Luteolina , Osteoporose , Feminino , Ratos , Animais , Reabsorção Óssea/patologia , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Farmacologia em Rede , Diferenciação Celular , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoporose/tratamento farmacológico , Fatores de Transcrição NFATC/metabolismo
7.
World Neurosurg ; 184: e76-e83, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38224906

RESUMO

OBJECTIVE: The purpose of this study was to explore the optimal timing and associated risks of pediatric spinal deformity surgery during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: All consecutive surgical cases for spinal deformity between September 2022 and May 2023 were included. The population was divided into several categories according to the time from diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to the day of surgery. Postoperative complications were analyzed using logistic regression, and we simultaneously showed the results from the crude model, minimally adjusted model, and fully adjusted model. RESULTS: A total of 81 consecutive patients were enrolled. In the fully adjusted model, compared with pre-COVID-19 patients, peri-COVID-19 patients had a 4.5-fold increased risk of postoperative complications (odds ratio = 5.5, 95% confidence interval 1.1-27.2, P = 0.037), early post-COVID-19 patients had a 2.3-fold increased risk (odds ratio= 3.3, 95% confidence interval 0.7-16.1, P = 0.133), and late post-COVID-19 patients were at essentially equal risk. In asymptomatic population, early post-COVID-19 patients and late post-COVID-19 patients appeared to be at equal risk compared with pre-COVID-19 patients. For patients with persistent symptoms, is necessary to wait at least 8 weeks or even longer after SARS-CoV-2 infection. Interaction tests demonstrated that the effect of the timing of surgery on postoperative complications significantly differed in populations with different symptoms. CONCLUSIONS: Surgery for pediatric spinal deformity should be postponed until 8 weeks after SARS-CoV-2 infection in cases with COVID-19-related symptoms within 2 weeks prior to surgery; whereas, for those who are asymptomatic within 2 weeks prior to surgery, an interval of 4 weeks seemed to be sufficient.


Assuntos
COVID-19 , Humanos , Criança , SARS-CoV-2 , Estudos Prospectivos , Complicações Pós-Operatórias/epidemiologia , Razão de Chances
8.
J Leukoc Biol ; 115(5): 946-957, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38266238

RESUMO

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro-computed tomography and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1-/- group produced more tartrate-resistant acid phosphatase-positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.


Assuntos
Ferroptose , Fator 2 Relacionado a NF-E2 , Osteoclastos , Osteogênese , Ligante RANK , Transdução de Sinais , Animais , Feminino , Camundongos , Reabsorção Óssea/patologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/genética , Diferenciação Celular , Ferroptose/genética , Técnicas de Silenciamento de Genes , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/patologia , Osteoporose/genética , Osteoporose/metabolismo , Ligante RANK/metabolismo , Células RAW 264.7
9.
Am J Infect Control ; 52(6): 644-649, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38232902

RESUMO

BACKGROUND: To examine the influence of early mobilization on the risk of surgical site infections (SSI) in patients undergoing spinal fusion surgery. METHODS: The retrospective cohort consisted of all consecutive patients who underwent spinal fusion surgery at our institution. For each case of SSI, 2 control patients without SSI at the corresponding index date were selected. Mobilization was predefined as "delayed" if it occurred more than 36 hours postoperatively. To account for potential confounding variables, we performed further adjustments using conditional logistic regression models. Subgroup analyses were conducted to evaluate the robustness of the statistical associations. RESULTS: Following the predefined statistical protocol and matching criteria, we matched 236 control cases to the SSI cases. Upon adjustment for confounding factors, our findings revealed that the risk of SSI was 120% higher in the group beginning mobilization more than 36 hours after surgery compared to the group beginning mobilization within 36 hours postoperatively (odds ratio = 2.206, 95% confidence interval 1.169-4.166, P = .015). In subgroup analyses, this statistical trend remained consistent. CONCLUSIONS: Early mobilization within 36 hours following spinal fusion surgery significantly reduces the risk of SSI. This pattern of reduced risk remains consistent among patients with degenerative diseases or spinal deformities.


Assuntos
Deambulação Precoce , Fusão Vertebral , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Fusão Vertebral/efeitos adversos , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Incidência , Adulto , Idoso de 80 Anos ou mais
10.
Transl Res ; 268: 28-39, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38280546

RESUMO

Tyrosine kinase inhibitors (TKIs) are frequently utilized in the management of malignant tumors. Studies have indicated that anlotinib has a significant inhibitory effect on oral squamous cell carcinoma (OSCC). However, the mechanisms underlying the development of resistance with long-term anlotinib treatment remain obscure. Our research found that METTL1 expression was heightened in anlotinib-resistant OSCC cells. We observed that METTL1 played a role in fostering resistance to anlotinib in both transgenic mouse models and in vitro. Mechanistically, the elevated METTL1 levels in anlotinib-resistant OSCC cells contributed to enhanced global mRNA translation and stimulated oxidative phosphorylation (OXPHOS) through m7G tRNA modification. Bioenergetic profiling demonstrated that METTL1 drived a metabolic shift from glycolysis to OXPHOS in anlotinib-resistant OSCC cells. Additionally, inhibition of OXPHOS biochemically negated METTL1's impact on anlotinib resistance. Overall, this study underscores the pivotal role of METTL1-mediated m7G tRNA modification in anlotinib resistance and lays the groundwork for novel therapeutic interventions to counteract resistance in OSCC.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Indóis , Metiltransferases , Neoplasias Bucais , Quinolinas , RNA de Transferência , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , Indóis/farmacologia , Quinolinas/farmacologia , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , RNA de Transferência/metabolismo , RNA de Transferência/genética , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Camundongos Transgênicos , Fosforilação Oxidativa/efeitos dos fármacos , Reprogramação Metabólica
11.
J Bone Joint Surg Am ; 106(4): 304-314, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38113312

RESUMO

BACKGROUND: Congenital early-onset scoliosis (CEOS) is characterized by a spectrum of vertebral anomalies, including formation failures and segmentation failures at the apex segment, which makes CEOS different from other etiologies of early-onset scoliosis. To date, studies on patients who have graduated from CEOS treatment using traditional dual growing rods (TDGR) have been scarce, and the preliminary results of TDGR with or without the apical control technique (ACT) have varied. We therefore compared the final outcomes of patients with CEOS who graduated from TDGR with or without the ACT. METHODS: A retrospective study of patients with CEOS who had graduated from TDGR treatment performed from 2007 to 2020 was conducted. Graduation included final fusion or observation after reaching skeletal maturity. Patients were divided into the ACT-TDGR group (apical vertebrectomy and/or hemivertebrectomy with short fusion and TDGR) and the TDGR-only group. Demographic characteristics, radiographic data, patient-reported clinical outcomes, pulmonary function, and complications were analyzed. RESULTS: A total of 41 patients with CEOS were enrolled: 13 in the ACT-TDGR group and 28 in the TDGR-only group. The lengthening intervals were longer in the ACT-TDGR group (mean [and standard deviation], 1.26 ± 0.66 years) than in the TDGR-only group (0.80 ± 0.27 years). The preoperative main curve was larger in the ACT-TDGR group (80.53° ± 19.50°) than in the TDGR-only group (64.11° ± 17.50°). The residual curve was comparable between groups (26.31° ± 12.82° in the ACT-TDGR group compared with 27.76° ± 15.0° in the TDGR group) at the latest follow-up. The changes in apical vertebral rotation and thoracic rotation were significantly larger in the ACT-TDGR group. Patients had comparable T1-12 and T1-S1 heights, pulmonary function, and 22-item Scoliosis Research Society (SRS-22) scores at the latest follow-up. The mean number of mechanical-related complications per patient was lower in the ACT-TDGR group (0.77 ± 0.73) than in the TDGR-only group (1.54 ± 1.43). Seventeen patients underwent final fusion. CONCLUSIONS: In this small-scale study, we observed that both ACT-TDGR and TDGR-only could correct the deformity while allowing for spinal growth in patients with CEOS. ACT-TDGR yielded better correction in severe cases and did not have a deleterious effect on spinal height. A large number of cases will be needed to validate the clinical value of the ACT. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Escoliose , Fusão Vertebral , Humanos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Fusão Vertebral/métodos , Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia
12.
World J Gastroenterol ; 29(45): 5974-5987, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38130998

RESUMO

BACKGROUND: Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2. AIM: To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment. METHODS: Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo. RESULTS: The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab. Thioridazine demonstrated the ability to directly bind to Skp2, resulting in a reduction in Skp2 expression at both the transcriptional and translational levels. Moreover, thioridazine effectively inhibited cell proliferation, exhibited antiapoptotic properties, and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways. The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo, surpassing the efficacy of either monotherapy. CONCLUSION: Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance, particularly when used in conjunction with lapatinib. This compound has potential benefits for patients with Skp2-proficient tumors.


Assuntos
Neoplasias Gástricas , Tioridazina , Humanos , Animais , Camundongos , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Lapatinib/farmacologia , Lapatinib/uso terapêutico , Tioridazina/farmacologia , Tioridazina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Camundongos Nus , Receptor ErbB-2/metabolismo , Proliferação de Células , Glicólise , Lactatos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Mamíferos
13.
J Orthop Surg Res ; 18(1): 904, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017583

RESUMO

PURPOSE: The purpose of the study was to evaluate the clinical efficacy and safety of using Ponte osteotomy combined with posterior lumbar interbody fusion in the treatment of patients with degenerative scoliosis. METHOD: The medical records and imaging data of degenerative scoliosis patients in our department from 2013 to 2022 were retrospectively collected. A total of 47 patients were included, including 16 male patients and 31 female patients. The mean follow-up was 47.8 months. Whole spine X-rays in the standing position were performed on all patients preoperatively, postoperatively, and at the latest follow-up. The length of hospital stay, complications, operative duration, estimated blood loss, instrumented segment, fused segment, clinical scores, and various radiological indicators were recorded. RESULTS: The coronal vertical axis improved from 3.1 ± 1.9 cm preoperatively to 1.2 ± 1.0 cm postoperatively with an average reduction of 1.9 ± 1.7 cm. The preoperative coronal Cobb angle was 18.1 ± 10.6°, the immediate postoperative Cobb angle was 6.6 ± 3.9°, and the Cobb angle at the last follow-up was 5.8 ± 3.7°. The sagittal vertical axis decreased from 5.6 ± 3.7 cm preoperatively to 2.7 ± 1.9 cm immediately after the operation and was well maintained at the last follow-up (3.1 ± 2.5 cm). Lumbar lordosis increased from 22.2 ± 10.2° preoperatively to 40.4 ± 8.3° postoperatively and 36.0 ± 8.8° at the last follow-up. The ODI score, VAS low back pain score, and VAS leg pain score were also improved to varying degrees. CONCLUSION: Ponte osteotomy combined with posterior lumbar interbody fusion can significantly improve coronal and sagittal plane deformities and postoperative functional scores in patients with adult degenerative scoliosis.


Assuntos
Dor Lombar , Escoliose , Fusão Vertebral , Adulto , Humanos , Masculino , Feminino , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do Tratamento
14.
Nutrients ; 15(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38004165

RESUMO

Our aim was to ascertain whether the prognostic nutritional index (PNI), could predict the health-related quality of life (HRQOL) in patients with adult degenerative scoliosis (ADS) undergoing corrective surgery. We conducted a retrospective analysis of consecutive patients diagnosed with ADS between January 2013 and June 2021. Three nutritional parameters were employed for analysis (PNI, anemia, and hypoalbuminemia). We utilized the Scoliosis Research Society-22 (SRS-22) questionnaire and the Oswestry Disability Index (ODI) questionnaire to assess clinical outcomes. Following the epidemiology guidelines, we presented results from three different models: the crude model, minimally adjusted model, and fully adjusted model. A total of 316 ADS patients were included in the statistical analysis. There was no significant difference in sagittal plane radiographic parameters between the two groups. After adjusting for important confounding factors, PNI was an independent predictor of postoperative HRQOL. Specifically, for each one-unit increase in PNI, there was an approximately 20% higher likelihood of patients achieving a better HRQOL. Furthermore, we did not observe an association between hemoglobin levels or albumin levels and HRQOL. In this study, PNI has been demonstrated to be correlated with the postoperative HRQOL in patients with ADS undergoing corrective surgery.


Assuntos
Lordose , Escoliose , Humanos , Adulto , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Lordose/cirurgia , Qualidade de Vida , Avaliação Nutricional , Estudos Retrospectivos , Prognóstico , Resultado do Tratamento
15.
Front Cell Dev Biol ; 11: 1282573, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965575

RESUMO

Growing rod implantation, a surgery treatment for EOS (early onset scoliosis), may cause a kind of chronic inflammation called metalosis and all other implant-related complications because of the metal debris released by the implants as a result of fraction and corrosion. There is no complete explanation of immunologic mechanisms of metalosis up to now. This review demonstrates the researches on metalosis from the clinical issues down to basic immunologic mechanisms. Adverse reactions of metal implants are mainly the formation of NLRP3 (nod-like receptor protein 3) inflammasome, primed by TLR4 (toll-like receptor protein 4), activated by phagocytosis and often accompanied by type Ⅳ hypersensitive reaction. Recent studies found that TNF-α (tumor necrosis factor α) also participates in priming, and activation of inflammasome requires disturbance of lysosome and release of cathepsin B. Ca-074Me and MCC950 are therapeutic interventions worth exploring in aseptic loosening of orthopedic implants.

16.
Hum Fertil (Camb) ; 26(4): 712-719, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37815345

RESUMO

The effect of the intramural fibroids not distorting the cavity remains controversial on implantation and pregnancy. The aim of this study was to examine the impact of non-cavity distorting intramural fibroids on endometrium. Fifty-six women with non-cavity distorting intramural fibroid were recruited in this study. Paired endometrial specimens, one from beneath the fibroid (ipsilateral endometrium) and the other from the opposite side of uterine cavity, away from the fibroid (contralateral endometrium) were obtained 7-9 days after the luteinizing hormone surge in a natural cycle. Histological dating, Mucin1 and Glycodelin expression and uterine natural killer (uNK) cell density were compared between the paired samples. The median (IQR) H-score of Mucin1 staining in the ipsilateral luminal epithelium was 210% (142-230%), which was significantly (p < 0.05) higher than that of the contralateral luminal endometrium (157%, IQR 114-176%). There was no significant difference in Mucin1 expression in the glandular epithelium. There was no significant difference in Glycodelin expression in luminal and glandular epithelium, uNK cells density or histological dating results between the paired endometrial samples. In conclusion, it is uncertain whether the altered expression of Mucin1 in luminal epithelium alone may have impact on implantation when other markers are not changed.


Assuntos
Leiomioma , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Glicodelina/metabolismo , Leiomioma/metabolismo , Leiomioma/patologia , Implantação do Embrião , Endométrio/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
17.
Curr Med Chem ; 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37817519

RESUMO

Ferroptosis is a newly discovered non-apoptotic cell death whose key is lipid peroxidation. It has been reported that ferroptosis is involved in the occurrence and development of tumors and nervous system and musculoskeletal diseases. Cellular ferroptosis contributes to the imbalance of bone homeostasis and is involved in the development of osteoporosis; however, the detailed mechanism of which is still unclear though it may provide a new direction for anti-osteoporosis. The current drugs used in the treatment of osteoporosis, such as bisphosphonates and teriparatide, have many side effects, increasing people's search for natural compounds to treat osteoporosis. This review paper briefly summarizes the current research regarding the mechanisms of ferroptosis and natural anti-osteoporosis compounds targeting its pathway.

18.
Neurospine ; 20(3): 1061-1072, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37798998

RESUMO

OBJECTIVE: Based on traditional dual growing rods (TDGR), apical control techniques (ACTs) were introduced as adjuvant procedures to improve deformity correction at the apex segment in the treatment of early-onset scoliosis (EOS). We aimed to explore whether TDGR+ ACTs have different indications, attain more deformity correction, have negative effects on spinal growth, and have different complications. METHODS: Between 2004 and 2019, a retrospective study of EOS patients treated with TDGR with or without ACTs was conducted and divided into 3 groups: TDGR group; hybrid technique (HT) group: Vertebrectomy/hemivertebrectomy with short fusion and TDGR; ACPS group: apical convex control pedicle screws (ACPS) and TDGR. Demographic, radiographic parameters, clinical outcomes, complications, and revisions were analyzed and compared. RESULTS: Seventy-eight EOS patients were enrolled. The preoperative main curve was the largest in the HT group. ACPS group had the smallest residual curve (19° ± 8.9°) and apical vertebral translation (12.0 ± 9.0 mm) at the latest follow-up, followed by the HT group (30° ± 17.4°, 22.1 ± 13.4 mm) and TDGR group (30° ± 13.2°, 32.8 ± 17.1 mm). ACPS group had the largest T1-12 height and T1-S1 height after index surgery. Complications and revisions in the ACTs groups was lower than the TDGR group. Scoliosis Research Society-22 self-image questionnaire was superior in the ACPS group. CONCLUSION: According to our intermediate results, TDGR+ACTs could improve correction ability of apex deformity. ACTs had little deleterious effects on spinal height during the lengthening procedures, with a lower complication rate than TDGR. TDGR+ACTs might be a supplemental option for suitable EOS patients.

19.
J Orthop Surg Res ; 18(1): 753, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794490

RESUMO

OBJECTIVE: The literature currently available on the characteristics of patients who require intensive care unit (ICU) admission after correction surgery for adult spinal deformity is lacking; this study aimed to identify risk factors for postoperative ICU admission following correction surgery for adult spinal deformity. METHODS: A retrospective review of patients who underwent primary posterior-based spinal fusion from 2015 to 2023 was performed. According to the ward they returned to, patients were further divided into an ICU group and a non-ICU group. Univariate and multivariate analyses were performed to evaluate preoperative and perioperative parameters to identify independent risk factors for postoperative ICU admission in adult spinal deformity patients. RESULTS: A total of 274 patients were included, including 115 males (41.97%) and 159 females (58.03%). The mean age of the patients was 32.00 ± 11.16 years (19-77 years). Following adjusted analysis, the preoperative and perioperative factors that were independently associated with ICU admission were age, body mass index ≥ 28 kg/m2, neuromuscular spinal deformity, respiratory disease, grade III-IV American Society of Anesthesiologists (ASA) classification, a scoliosis Cobb angle ≥ 90°, a kyphosis Cobb angle ≥ 90°, and ≥ 12 fused segments. Compared with the non-ICU group, the ICU group had a higher incidence of complications, a longer hospital stay, and higher medical costs (P < 0.05). CONCLUSION: This study identified independent risk factors associated with postoperative ICU admission in adult spinal deformity patients; and explored relative measures to decrease or avoid the risk of postoperative ICU admission. Surgeons could use these data to develop and plan appropriate perioperative care processes in advance and provide consultation for family members before surgery.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Masculino , Feminino , Humanos , Adulto , Adulto Jovem , Resultado do Tratamento , Escoliose/etiologia , Cifose/cirurgia , Estudos Retrospectivos , Fatores de Risco , Unidades de Terapia Intensiva , Fusão Vertebral/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
20.
J Orthop Surg Res ; 18(1): 564, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537614

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic condition characterized by the disruption of blood supply to the femoral head, leading to ischemia of internal tissues, subchondral bone fractures, necrosis, and eventual collapse of the weight-bearing portion of the femoral head. This condition results in severe functional impairment, pain, and even disability of the hip joint. Existing animal models of ONFH have limitations in replicating the natural disease progression accurately. Thus, there is a critical need to develop a novel animal model capable of better simulating localized pressure on the human femoral head to facilitate ONFH-related research. METHODS: In this study, we present a novel approach for modeling ONFH, which involves integrating stress factors into the modeling process through the utilization of 3D printing technology and principles of biomechanics. A total of 36 animals were randomly assigned to six groups, where they received either the novel modeling technique or the traditional hormone induction method. Subsequently, an 8-week treatment period was implemented, followed by conducting micro-CT scans and histological evaluations to assess tissue outcomes. RESULTS: The study evaluated the cytotoxicity of the material used in the new model, and it was observed that the material did not exhibit any cytotoxic effects on cells. Additionally, the novel model successfully replicated the pathological features of ONFH, including femoral head collapse, along with a substantial presence of empty bone lacunae, cartilage defects, and subchondral bone fractures in the subchondral bone region. CONCLUSION: In conclusion, our study provides evidence that the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem.


Assuntos
Necrose da Cabeça do Fêmur , Fraturas Ósseas , Osteonecrose , Animais , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/patologia , Fraturas Ósseas/patologia , Impressão Tridimensional , Microtomografia por Raio-X
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