RESUMO
Osteoarthritis (OA) is a prevalent degenerative condition commonly observed in the elderly, leading to consequential disability. Despite notable advancements made in clinical strategies for OA, its pathogenesis remains uncertain. The intricate association between OA and metabolic processes has yet to receive comprehensive exploration. In our investigation, we leveraged public databases and applied machine learning algorithms, including WGCNA, LASSO, RF, immune infiltration analysis, and pathway enrichment analysis, to scrutinize the role of lipid metabolism-associated genes (LAGs) in the OA. Our findings identified three distinct biomarkers, and evaluated their expression to assess their diagnostic value in the OA patients. The exploration of immune infiltration in these patients revealed an intricate relationship between immune cells and the identified biomarkers. In addition, in vitro experiments, including qRT-PCR, Western blot, chondrocyte lipid droplets detection and mitochondrial fatty acid oxidation measurement, further verified abnormal expressions of selected LAGs in OA cartilage and confirmed the correlation between lipid metabolism and OA.
Assuntos
Biomarcadores , Metabolismo dos Lipídeos , Aprendizado de Máquina , Osteoartrite , Humanos , Metabolismo dos Lipídeos/genética , Osteoartrite/genética , Osteoartrite/imunologia , Osteoartrite/metabolismo , Biomarcadores/metabolismo , Algoritmos , Condrócitos/metabolismo , Condrócitos/imunologiaRESUMO
BACKGROUND: Anterior cervical discectomy and fusion surgery (ACDF) is a common technique in treating degenerative cervical spondylosis. This study is to evaluate the changes of cervical muscles after ACDF and analyze the correlation between related muscle changes and clinical efficacy. METHODS: Sixty-five postoperative patients (single-level ACDF) with cervical spondylotic myelopathy from January 2013 to December 2022 were analyzed. The measured parameters include: the axial section of longus colli cross-sectional area (AxCSA), the volume of cervical longus, the ratio of long and short diameter line (RLS), the cervical extensor cross-sectional area (CESA), the vertebral body area (VBA), and the CESA/VBA. The visual analog scale (VAS), modified Japanese Orthopedic Association score (mJOA), and neck disability index (NDI) were evaluated. The changes in muscle morphology were analyzed, and the correlation analysis was conducted between morphological changes and function scores. RESULTS: The postoperative AxCSA of surgical segment (3rd month, 12th month, and the last follow-up) was decreased compared to preoperative (141.62 ± 19.78), and the differences were significant (P < 0.05). The corresponding data reduced to (119.42 ± 20.08) mm2, (117.59 ± 19.69) mm2, and (117.41 ± 19.19) mm2, respectively (P < 0.05). The RLS increased, and the volume of cervical longus decreased significantly after surgery (P < 0.05). Negative correlation was found between postoperative volume of cervical longus and VAS at the 3rd month (r = - 0.412), 12th month (r = - 0.272), and last follow-up (r = - 0.391) (P < 0.05). Negative correlation existed between postoperative volume of cervical longus and NDI at the 3rd month (r = - 0.552), 12th month (r = - 0.293), and last follow-up (r = - 0.459) (P < 0.05). CONCLUSION: The volume of cervical longus decreased and its morphology changed after ACDF surgery. The mainly affected muscle was the cervical longus closing to the surgical segment. Negative correlation was found between the postoperative volume of cervical longus and function scores (VAS and NDI).
Assuntos
Fusão Vertebral , Espondilose , Humanos , Fusão Vertebral/métodos , Estudos Retrospectivos , Discotomia/métodos , Pescoço/cirurgia , Resultado do Tratamento , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Espondilose/diagnóstico por imagem , Espondilose/cirurgia , MúsculosRESUMO
OBJECTIVE: This study aims to compare the clinical effects and imaging data of patients who underwent endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) with those who received unilateral biportal endoscopic lumbar interbody fusion (ULIF). METHODS: A retrospective analysis was conducted on the clinical data of 69 patients presenting with typical intermittent claudication and signs and symptoms indicative of unilateral lower extremity nerve root compression, meeting inclusion criteria between April 2022 and June 2022. Among the cohort, 35 patients underwent ULIF group, while 34 patients underwent Endo-TLIF group. We compared perioperative parameters, including intraoperative blood loss, duration of hospital stay, and operation time between the two groups. Pre-operative and post-operative changes in the height and cross-sectional area of the target intervertebral space were also compared between the groups. Finally, we evaluated bone graft size and interbody fusion rates at 6 and 12 months post-surgery using the Brantigan scoring system. RESULTS: The ULIF group had significantly shorter operative times compared to the Endo-TLIF group (P < 0.05). Conversely, the Endo-TLIF group exhibited significantly shorter hospital stays compared to the ULIF group (P < 0.05). However, there were no significant differences in intraoperative bleeding between the two groups (P > 0.05). Furthermore, both groups exhibited postoperative increases in vertebral canal volume compared to baseline (P < 0.05), with no significant difference in the change in the cross-sectional area of the target intervertebral space between the two surgical methods (P > 0.05). Interbody fusion rates were comparable between the two groups at both 6 and 12 months after surgery (P > 0.05). Lastly, the ULIF group had a significantly larger area of bone graft than the Endo-TLIF group (P < 0.05). CONCLUSION: In summary, the ULIF technique, as a novel spinal endoscopy approach, is a safer and more effective minimally invasive surgical method for addressing lumbar spinal stenosis and intervertebral disc herniation in patients. Both surgical methods have their own advantages and drawbacks. With the development of technology and related instruments, the limitations of both techniques can be mitigated for to a certain extent, and they can be applied by more doctors in diverse medical fields in the future.
Assuntos
Deslocamento do Disco Intervertebral , Fusão Vertebral , Estenose Espinal , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do Tratamento , Fusão Vertebral/métodos , Endoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
Rheumatoid arthritis (RA) is an autoimmune rheumatic disease, which do not respond well to current treatment partially. Therefore, further in-depth elucidation of the molecular mechanism and pathogenesis of RA is urgently needed for the diagnosis, personalized therapy and drug development. Herein, we collected 111 RA samples from Gene Expression Omnibus (GEO) database, and conducted differentially expressed genes and GESA analysis. Abnormal activation and imbalance of immune cells in RA were observed. WGCNA was utilized to explore the gene modules and CD8+ T cell-related genes (CRGs) were chosen for KEGG and GO analysis. Besides, to explore biomarkers of RA in depth, machine learning algorithms and bioinformatics analysis were used, and we identified GDF15, IGLC1, and IGHM as diagnostic markers of RA, which was confirmed by clinical samples. Next, ssGSEA algorithms were adopted to investigate the differences in immune infiltration of 23 immune cell subsets between RA and healthy control group. Finally, optimal classification analysis based on consensus clustering combined with ssGSEA algorithms were conducted. GDF15 was revealed that to be positively correlated with mast cells and type 2 T helper cells, but negatively correlated with most other immune cells. On the other hand, IGHM and IGLC1 were negatively correlated with CD56dim natural killer cells, while positively associated with other immune cells. Finally, RA samples in subtype A exhibited a higher immune infiltration status. This study could provide guidance for individualized treatment of RA patients and provide new targets for drug design.
Assuntos
Artrite Reumatoide , Doenças Autoimunes , Humanos , Artrite Reumatoide/genética , Linfócitos T CD8-Positivos , Algoritmos , Biomarcadores , Biologia ComputacionalRESUMO
Objective: To compare the effectiveness between unilateral biportal endoscopic lumbar interbody fusion (ULIF) and endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) in treatment of lumbar spinal stenosis combined with intervertebral disc herniation. Methods: A clinical data of 64 patients with lumbar spinal stenosis and intervertebral disc herniation, who were admitted between April 2020 and November 2021 and met the selection criteria, was retrospectively analyzed. Among them, 30 patients were treated with ULIF (ULIF group) and 34 patients with Endo-TLIF (Endo-TLIF group). There was no significant difference in baseline data such as gender, age, disease duration, lesion segment, preoperative visual analogue scale (VAS) score of low back pain and leg pain, Oswestry disability index (ODI), spinal canal area, and intervertebral space height between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stays, and postoperative complications were compared between the two groups, as well as the VAS scores of low back pain and leg pain, ODI, and imaging measurement indicators (spinal canal area, intervertebral bone graft area, intervertebral space height, and degree of intervertebral fusion according to modified Brantigan score). Results: Compared with the Endo-TLIF group, the ULIF group had shorter operation time, but had more intraoperative blood loss and longer hospital stays, with significant differences ( P<0.05). The cerebrospinal fluid leakage occurred in 2 cases of Endo-TLIF group and 1 case of ULIF group, and no other complication occurred. There was no significant difference in the incidence of complications between the two groups ( P>0.05). All patients in the two groups were followed up 12 months. The VAS scores of lower back pain and leg pain and ODI in the two groups significantly improved when compared with those before operation ( P<0.05), and there was no significant difference between different time points after operation ( P>0.05). And there was no significant difference between the two groups at each time point after operation ( P>0.05). Imaging examination showed that there was no significant difference between the two groups in the change of spinal canal area, the change of intervertebral space height, and intervertebral fusion rate at 6 and 12 months ( P>0.05). The intervertebral bone graft area in the ULIF group was significantly larger than that in the Endo-TLIF group ( P<0.05). Conclusion: For the patients with lumbar spinal stenosis combined with intervertebral disc herniation, ULIF not only achieves similar effectiveness as Endo-TLIF, but also has advantages such as higher decompression efficiency, flexible surgical instrument operation, more thorough intraoperative intervertebral space management, and shorter operation time.
Assuntos
Deslocamento do Disco Intervertebral , Dor Lombar , Fusão Vertebral , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Dor Lombar/etiologia , Dor Lombar/cirurgia , Perda Sanguínea Cirúrgica , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Estudos RetrospectivosRESUMO
There is no effective treatment for peripheral nerve injury-induced chronic neuropathic pain (NP), which profoundly impacts the quality of life of those affected. Transmembraneprotein100 (TMEM100) is considered to be a pain regulatory protein and is expressed in the dorsal root ganglion (DRG) of rats. However, the mechanism of pain regulation and the expression of TMEM100 following various peripheral nerve injuries are unclear. In this study, we constructed two pain models of peripheral nerve injury: tibial nerve injury (TNI) and chronic constriction injury (CCI). This study found that the Paw Withdrawal Mechanical Threshold (PWMT) and Paw Withdraw Thermal Latency (PWTL) of the rats in the two pain models decreased significantly, and the expression of TMEM100 in the DRG of two groups also decreased significantly. Furthermore, the decrease in the CCI group was more obvious than in the TNI group. There was no significant statistical significance (P > 0.05). We constructed an adeno-associated virus 6 (AAV6) vector expressing recombinant fluorescent TMEM100 protein and injected it into the sciatic nerve (SN) of two pain models: CCI and TNI. PWMT and PWTL were significantly increased in the two groups, along with the expression of TMEM100 in the spinal cord and DRG. It also significantly inhibited the activation of microglia, astrocytes, and several inflammatory mediators (TNF- α, IL-1 ß, and IL-6). In summary, the results of this study suggested that TMEM100 might be a promising molecular strategy for the treatment of NP, and its anti-inflammatory effects might play an important role in pain relief.
Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Ratos Sprague-Dawley , Traumatismos dos Nervos Periféricos/metabolismo , Qualidade de Vida , Medula Espinal/metabolismo , Neuralgia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Hiperalgesia/metabolismoRESUMO
Mammalian cells can turn over peroxisomes through Stub1-mediated pexophagy. The pathway potentially permits cellular control of the quantity and quality of peroxisomes. During this process, heat shock protein 70 and the ubiquitin E3 ligase, Stub1, translocate onto peroxisomes to be turned over to initiate pexophagy. The Stub1 ligase activity allows the accumulation of ubiquitin and other autophagy-related modules on targeted peroxisomes. Elevating reactive oxygen species (ROS) levels within the peroxisomal lumen can activate Stub1-mediated pexophagy. One can, therefore, use dye-assisted ROS generation to trigger and monitor this pathway. This article outlines the procedures for using two classes of dyes, fluorescent proteins and synthetic fluorophores, to initiate pexophagy within mammalian cell cultures. These dye-assisted ROS generation-based protocols can not only be used to target all the peroxisomes within a cell population globally but can also permit the manipulation of individual peroxisomes within single cells. We also describe how Stub1-mediated pexophagy can be followed using live-cell microscopy.
Assuntos
Autofagia , Macroautofagia , Animais , Espécies Reativas de Oxigênio/metabolismo , Autofagia/fisiologia , Proteínas/metabolismo , Ubiquitina/metabolismo , Mamíferos/metabolismo , Peroxissomos/metabolismoRESUMO
Rheumatoid arthritis (RA) causes irreversible joint damage, but the pathogenesis is unknown. Therefore, it is crucial to identify diagnostic biomarkers of RA metabolism-related genes (MRGs). This study obtained transcriptome data from healthy individuals (HC) and RA patients from the GEO database. Weighted gene correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and random forest (RF) algorithms were adopted to identify the diagnostic feature biomarker for RA. In addition, biomarkers were verified by qRT-PCR and Western blot analysis. We established a mouse model of collagen-induced arthritis (CIA), which was confirmed by HE staining and bone structure micro-CT analysis, and then further verified the biomarkers by immunofluorescence. In vitro NMR analysis was used to analyze and identify possible metabolites. The correlation of diagnostic feature biomarkers and immune cells was performed using the Spearman-rank correlation algorithm. In this study, a total of 434 DE-MRGs were identified. GO and KEGG enrichment analysis indicated that the DE-MRGs were significantly enriched in small molecules, catabolic process, purine metabolism, carbon metabolism, and inositol phosphate metabolism. AKR1C3, MCEE, POLE4, and PFKM were identified through WGCNA, LASSO, and RF algorithms. The nomogram result should have a significant diagnostic capacity of four biomarkers in RA. Immune infiltration landscape analysis revealed a significant difference in immune cells between HC and RA groups. Our findings suggest that AKR1C3, MCEE, POLE4, and PFKM were identified as potential diagnostic feature biomarkers associated with RA's immune cell infiltrations, providing a new perspective for future research and clinical management of RA.
Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Camundongos , Mapeamento Cromossômico , Aprendizado de Máquina , Algoritmos , Artrite Experimental/genética , Artrite Reumatoide/genética , BiomarcadoresRESUMO
Background: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics. Methods: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways. Results: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation. Conclusion: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.
RESUMO
OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.
Assuntos
Peróxido de Hidrogênio , Músculo Liso Vascular , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/metabolismo , Músculo Liso Vascular/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 3/farmacologia , Caspase 9/metabolismo , Caspase 9/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Apoptose/genética , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologiaRESUMO
Objective: To assess the economic evaluation of margetuximab plus chemotherapy over trastuzumab plus chemotherapy for women with pretreated ERBB2-positive advanced breast cancer in the United States (US) and China. Methods: Based on the SOPHIA trial, a three-state Markov model was developed to compare the cost and efficacy of margetuximab to trastuzumab for previously treated women with ERBB2-positive advanced breast cancer. The model inputs were derived from existing literature and the US life table. Primary outcomes included lifetime costs in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty. Results: The base case analyses demonstrated that margetuximab plus chemotherapy had an increasing cost of $68,132 and $20,540 over trastuzumab plus chemotherapy in the US and China, respectively, with a gain of 0.11 and 0.09 QALYs both favored margetuximab. The ICERs for two treatment strategies were $260,176 in the US and $630,777 in China, resulting in a poor cost-effectiveness at their respective threshold of willingness to play. One-way sensitivity analyses showed that the results to be most sensitive to the price of margetuximab and that of trastuzumab. And an 11 and 82% price reduction of margetuximab would make this regimen cost-effective in the US and China, respectively. Conclusion: In the US and China, margetuximab plus chemotherapy is not likely to be cost-effective for women with pretreated ERBB2-positive advanced breast cancer, whereas price reduction effectively improves insufficient cost-effectiveness.
Assuntos
Neoplasias da Mama , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Feminino , Humanos , Cadeias de Markov , Receptor ErbB-2/uso terapêutico , Trastuzumab/uso terapêutico , Estados UnidosRESUMO
BACKGROUND: Although the oral microbiome plays an important role in the progression of oral diseases, the microbes closely related to these diseases remain largely uncharacterized. RESULTS: We collected saliva samples from 140 individuals and performed 16 S amplicon sequencing. An interpretable machine learning framework for imbalanced high-dimensional big data of clinical microbial samples was developed to identify 14 oral microbiome features associated with oral diseases. Microbiome risk scores (MRSs) with the identified features were constructed with SHapley Additive exPlanations (SHAP). Correlations of the MRSs with individual physiological indicators and lifestyle habits were calculated. CONCLUSION: Our results reveal a set of oral microbiome features associated with oral diseases. Our study demonstrates the feasibility of preventing oral disease through lifestyle interventions and provides a reference method for the era of precision medicine aimed at individualized medicine.
Assuntos
Aprendizado de Máquina , Microbiota , Humanos , Microbiota/genéticaRESUMO
Taking advantage of chiral ionic liquids, this study deals with the improvement of the enantioseparation performance of a traditional chiral selector (maltodextrin) in capillary electrophoresis. Herein, two polyhydroxy compound-based chiral ionic liquids, namely tetramethylammonium-D-gluconic acid and tetramethylammonium-shikimic acid were designed and utilized as additives for chiral separation for the first time. The synergistic systems provided much better enantioseparations of twelve model drugs compared to the single maltodextrin system. These model analytes contained analgesics, antidepressants, antiallergic drugs, antifungal drugs, antihypertensive drugs, and antiparkinsonian drugs. After optimizing the separation conditions, the chiral recognition mechanism was probed by means of ultraviolet spectroscopy, nuclear magnetic resonance, and molecular modeling. The results of spectroscopic and computational analyses were in good consistency with enantioseparation outcomes. Finally, the proposed method was successfully used for the determination of the enantiomeric purity of duloxetine hydrochloride.
Assuntos
Antialérgicos , Líquidos Iônicos , Antifúngicos , Anti-Hipertensivos , Cloridrato de Duloxetina , Eletroforese Capilar/métodos , Líquidos Iônicos/química , Polissacarídeos , Compostos de Amônio Quaternário , Ácido Chiquímico , EstereoisomerismoRESUMO
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Figs. 3B and 5C were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 42934300, 2017; DOI: 10.3892/mmr.2017.7103].
RESUMO
BACKGROUND: Recently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, its role in lung adenocarcinoma (LUAD) has not been reported until now. METHODS: The expression of PAFAH1B3 in LUAD was determined by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) analyses. A chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyze the prognostic value of PAFAH1B3. The CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and the cell cycle. The xenograft tumor model was constructed to explore the function of PAFAH1B3 in vivo. Western blot and IHC analyses were performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) and IHC analyses were used to analyze the effect of PAFAH1B3 on immune cell infiltration. RESULTS: Our study showed that the expression of PAFAH1B3 was upregulated in LUAD tissues and cells compared with noncancerous tissues and cells. Additionally, the results indicated that the expression of PAFAH1B3 was positively correlated with distant metastasis, TNM stage and poor clinical outcome and it was an independent prognostic risk factor for LUAD. In addition, silencing PAFAH1B3 suppressed cell proliferation, colony formation, and invasion and increased the cell population in the G0-G1 phases in vitro. Furthermore, our results showed that knockdown of PAFAH1B3 increased the epithelial marker E-cadherin level and decreased the mesenchymal marker N-cadherin level in vitro and in vivo. We also proved that PAFAH1B3 downregulation inhibited tumorigenesis and neutrophil infiltration in the xenograft tumor model. CONCLUSION: Our studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , PrognósticoRESUMO
The rapid development of portable electronics has contributed to an urgent demand for versatile and flexible electrodes of wearable energy storage devices and pressure sensors. We fabricate a stretchable electrode by coupling the nickel-cobalt sulfide (NiCoS) nanosheet layer with Ag@NiCo nanowire (NW) networks. NiCoS wrinkled nanostructure, highly conductive networks, and intense interactions between substrate/networks and active materials/networks endow the electrodes with excellent energy storage capacity, superior electrochemical/mechanical stability, and good conductivity. A high-performance asymmetric supercapacitor is developed using the composite electrode. It operates in a wide potential window of 1.4 V and achieves a maximum energy density of 40.0 W h kg-1 at a power density of 1.1 kW kg-1; it also exhibits excellent mechanical flexibility and good waterproof performance. Moreover, a sandwiched capacitive pressure sensor constructed using the same electrodes has a wide sensing range (up to 260 kPa), low detection limit (â¼47 mN), fast response (â¼66 ms), and excellent mechanical stability (10 000 cycles). This study demonstrates that the appropriate design of the functional electrode facilitates the construction of various high-performance devices, denoting the versatility of our electrodes in the development of wearable electronics.
RESUMO
Objective: Through the follow-up analysis of cervical spine fracture cases with ankylosing spondylitis (AS), a treatment-oriented fracture classification method is introduced to evaluate the clinical efficacy guided by this classification method. Method: A retrospective analysis was performed on 128 AS patients who underwent comprehensive treatment in the Spine Surgery Department of Qingdao University Hospital from January 2009 to May 2018. Statistics of patient demographic data, distribution of different fractures corresponding to surgical methods, 3-year follow-up outcomes, and summary of objective fracture classification methods were analyzed. A prospective 5-year follow-up study of 90 patients with AS cervical spine fractures from June 2015 to August 2020 was also included. Statistical differences on the distribution of factors such as case information, cervical spine sagittal sequence parameters, and fracture classification were assessed. Correlations between surgical information, American Spinal Injuries Association grade (ASIA), modified Japanese Orthopaedic Association scores (mJOA), and other factors were analyzed to establish a nomogram predictive model for curative effect outcomes. Overall, three major types and the four subtypes of AS cervical spine fractures were evaluated based on the clinical efficacy of the classification and the selection of surgical treatment methods. Result: The most common type of fracture was type II (30 cases, 33.33%), most of the subtypes were A (37 cases), followed by B (36 cases) and C (17 cases). Twenty-four of 28 patients with type I underwent anterior surgery, and 47 of 62 patients with type II and III underwent posterior surgery. The average follow-up time was 25.76 ± 11.80 months. The results of predicting clinical variables are different but include factors such as fracture type and subtype, type of operation, and age. The predictor variables include the above-mentioned similar variables, but survival is more affected by the fracture type of the patient. Conclusion: This predictive model based on follow-up information delineation points out the impact of ankylosing spondylitis cervical spine fracture classification on surgical selection and clinical efficacy.
Assuntos
Fraturas da Coluna Vertebral , Espondilite Anquilosante , Vértebras Cervicais/cirurgia , Seguimentos , Humanos , Nomogramas , Estudos Prospectivos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/cirurgia , Resultado do TratamentoRESUMO
Scrophulariae Radix is one of the widely used traditional Chinese medicines. In this study, a high-performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry method was established for the simultaneous determination of multiple bioactive constituents including four iridoid glycosides, two phenylpropanoid glycosides, six organic acids, 11 nucleosides and 16 amino acids in Scrophulariae Radix. The validated method was used to analyze nine Scrophulariae Radix samples processed by different processing methods. In addition, Grey relational analysis and DTOPSIS were used to evaluate the samples according to the content of 39 ayalytes. The results showed that the quality of Scrophulariae Radix processed by cutting into slices, sun drying and "sweating" methods were better. All the results proved that the developed method was available and could be used to evaluate the quality of Scrophulariae Radix.
Assuntos
Medicamentos de Ervas Chinesas , Scrophularia , Aminoácidos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Glicosídeos Iridoides/química , Nucleosídeos , Scrophularia/química , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: The current study aimed to explore the efficacy of Zero profile intervertebral fusion system (Zero-P) and traditional anterior plate cage system (PC) in the treatment of cervical spondylotic myelopathy (CSM). Further, the present study evaluated effects of the treatments on medical security, height of intervertebral disc, adjacent-level ossification development (ALOD), and adjacent segmentation disease (ASD) through a systematic retrospective analysis. METHODS: Studies on Zero-P system and traditional anterior plate cage system for ACDF in the treatment of CSM were searched in PubMed, Web of Science, Ovid, Embase, and Cochrane Library databases. Two independent researchers screened articles, extracted data, and evaluated the quality of the articles based on the inclusion and exclusion criteria of the current study. RevMan5.3 software was used for meta-analysis following the guidelines of Cochrane collaboration network. Cervical curvature, interbody fusion rate, preoperative and postoperative disc height index (DHI), fusion cage sinking rate, postoperative dysphagia, ASD, ALOD, and loosening of screw were compared between the two groups. RESULTS: A total of 17 literatures were included in the present study, including 6 randomized controlled trials and 11 observational studies. The studies comprised a total of 1204 patients with CSM, including 605 patients in the Zero-P system group (Zero-P group) and 599 patients in the traditional animal plate cage group (PC group). Results of this meta-analysis showed that postoperative dysphagia [OR = 0.40, CI (0.28, 95% 0.58), P < 0.00001], ALOD [OR = 0.09, CI (0.02, 95% 0.39), P = 0.001], ASD [OR = 0.42, CI (0.20, 95% 0.86), P = 0.02], and screw loosening [OR = 0.20, CI (0.08, 95% 0.52), P = 0.0009] of the Zero-P group were significantly lower compared with the PC group. On the other hand, preoperative cervical curvature [WMD = -0.23, CI (-1.38, 95% 0.92), P = 0.69], postoperative cervical curvature [WMD = -0.38, CI (-1.77, 95% 1.01), P = 0.59], cage sinking rate [OR = 1.41, CI [0.52, 95% 3.82], P = 0.50], intervertebral fusion rate [OR = 0.76, CI (0.27, 95% 2.48), P = 0.38], preoperative DHI [WMD = -0.04, CI (-0.14, 95% 0.22), P = 0.65], and postoperative DHI [WMD = 0.06, CI (-0.22, 95% 0.34), P = 0.675] were not significantly different between the two groups. CONCLUSION: It was evident that the Zero-P system used in ACDF is superior compared with the traditional anterior plate cage system in postoperative dysphagia, avoiding ALOD, ASD, and screw loosening.
Assuntos
Fusão Vertebral , Espondilose , Vértebras Cervicais/cirurgia , Discotomia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Espondilose/cirurgia , Resultado do TratamentoRESUMO
Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.